Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229–263 (2024).
Google ScholarÂ
Ling, H. et al. Junk DNA and the long non-coding RNA twist in cancer genetics. Oncogene 34, 5003–5011 (2015).
Google ScholarÂ
Liu, S. J., Dang, H. X., Lim, D. A., Feng, F. Y. & Maher, C. A. Long noncoding RNAs in cancer metastasis. Nat. Rev. Cancer 21, 446–460 (2021).
Google ScholarÂ
Anastasiadou, E., Jacob, L. S. & Slack, F. J. Non-coding RNA networks in cancer. Nat. Rev. Cancer 18, 5–18 (2017).
Google ScholarÂ
Goodall, G. J. & Wickramasinghe, V. O. RNA in cancer. Nat. Rev. Cancer 21, 22–36 (2021).
Google ScholarÂ
Anfossi, S., Babayan, A., Pantel, K. & Calin, G. A. Clinical utility of circulating non-coding RNAs — an update. Nat. Rev. Clin. Oncol. 15, 541–563 (2018).
Google ScholarÂ
Toden, S. & Goel, A. Non-coding RNAs as liquid biopsy biomarkers in cancer. Br. J. Cancer 126, 351–360 (2022).
Google ScholarÂ
Yamada, A. et al. A RNA-sequencing approach for the identification of novel long non-coding RNA biomarkers in colorectal cancer. Sci. Rep. 8, 575 (2018).
Google ScholarÂ
Bhan, A., Soleimani, M. & Mandal, S. S. Long noncoding RNA and cancer: a new paradigm. Cancer Res. 77, 3965–3981 (2017).
Google ScholarÂ
Mattick, J. S. et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat. Rev. Mol. Cell Biol. 24, 430–447 (2023).
Google ScholarÂ
Zhang, X. Z., Liu, H. & Chen, S. R. Mechanisms of long non-coding RNAs in cancers and their dynamic regulations. Cancers 12, 1245 (2020).
Google ScholarÂ
Yao, R.-W., Wang, Y. & Chen, L.-L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 21, 542–551 (2019).
Google ScholarÂ
Statello, L., Guo, C. J., Chen, L. L. & Huarte, M. Gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. Cell Biol. 22, 96–118 (2021).
Google ScholarÂ
Chen, Y. G., Satpathy, A. T. & Chang, H. Y. Gene regulation in the immune system by long noncoding RNAs. Nat. Immunol. 18, 962–972 (2017).
Google ScholarÂ
Yu, Z. et al. The role of tumor-derived exosomal LncRNA in tumor metastasis. Cancer Gene Ther. 32, 273–285 (2025).
Google ScholarÂ
Leucci, E., Coe, E. A., Marine, J. & Vance, K. W. The emerging role of long non-coding RNAs in cutaneous melanoma. Pigment Cell Melanoma Res. 29, 619–626 (2016).
Google ScholarÂ
Sarropoulos, I., Marin, R., Cardoso-Moreira, M. & Kaessmann, H. Developmental dynamics of lncRNAs across mammalian organs and species. Nature 571, 510–514 (2019).
Google ScholarÂ
Derrien, T. et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res. 22, 1775–1789 (2012).
Google ScholarÂ
Huarte, M. The emerging role of lncRNAs in cancer. Nat. Med. 21, 1253–1261 (2015).
Google ScholarÂ
Athie, A. et al. Analysis of copy number alterations reveals the lncRNA ALAL-1 as a regulator of lung cancer immune evasion. J. Cell Biol. 219, e201908078 (2020).
Google ScholarÂ
Carlevaro-Fita, J. et al. Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis. Commun. Biol. 3, 56 (2020).
Google ScholarÂ
Luo, J. et al. Long non-coding RNAs: a rising biotarget in colorectal cancer. Oncotarget 8, 22187–22202 (2017).
Google ScholarÂ
Shakhpazyan, N. K. et al. Long non-coding RNAs in colorectal cancer: navigating the intersections of immunity, intercellular communication, and therapeutic potential. Biomedicines 11, 2411 (2023).
Google ScholarÂ
Teng, L. et al. The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis. Nat. Commun. 12, 3734 (2021).
Google ScholarÂ
Engreitz, J. M. et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 539, 452–455 (2016).
Google ScholarÂ
Lin, C. et al. Transcriptional and posttranscriptional regulation of HOXA13 by lncRNA HOTTIP facilitates tumorigenesis and metastasis in esophageal squamous carcinoma cells. Oncogene 36, 5392–5406 (2017).
Google ScholarÂ
Dai, J. et al. LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer. Cell Death Dis. 14, 312 (2023).
Google ScholarÂ
Bridges, M. C., Daulagala, A. C. & Kourtidis, A. LNCcation: lncRNA localization and function. J. Cell Biol. 220, e202009045 (2021).
Google ScholarÂ
Schmitt, A. M. & Chang, H. Y. Long noncoding RNAs in cancer pathways. Cancer Cell 29, 452–463 (2016).
Google ScholarÂ
Werner, A., Kanhere, A., Wahlestedt, C. & Mattick, J. S. Natural antisense transcripts as versatile regulators of gene expression. Nat. Rev. Genet. 25, 730–744 (2024).
Google ScholarÂ
Herman, A. B., Tsitsipatis, D. & Gorospe, M. Integrated lncRNA function upon genomic and epigenomic regulation. Mol. Cell 82, 2252–2266 (2022).
Google ScholarÂ
Liu, Y. et al. The RP11-417E7.1/THBS2 signaling pathway promotes colorectal cancer metastasis by activating the Wnt/β-catenin pathway and facilitating exosome-mediated M2 macrophage polarization. J. Exp. Clin. Cancer Res. 43, 195 (2024).
Google ScholarÂ
Li, P. et al. lncRNA HOTAIR contributes to 5FU resistance through suppressing miR-218 and activating NF-κB/TS signaling in colorectal cancer. Mol. Ther. Nucleic Acids 8, 356–369 (2017).
Google ScholarÂ
Bhat, S. A. et al. Long non-coding RNAs: mechanism of action and functional utility. Noncoding RNA Res. 1, 43–50 (2016).
Google ScholarÂ
Wang, K. C. & Chang, H. Y. Molecular mechanisms of long noncoding RNAs. Mol. Cell 43, 904–914 (2011).
Google ScholarÂ
Yang, P. et al. CAF-derived exosomal WEE2-AS1 facilitates colorectal cancer progression via promoting degradation of MOB1A to inhibit the Hippo pathway. Cell Death Dis. 13, 796 (2022).
Google ScholarÂ
Peng, W. X., Koirala, P. & Mo, Y. Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene 36, 5661–5667 (2017).
Google ScholarÂ
Wang, R. et al. USP30-AS1 suppresses colon cancer cell inflammatory response through NF-κB/MYBBP1A signaling. Inflammation 48, 1998–2008 (2025).
Google ScholarÂ
Hung, T. et al. Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat. Genet. 43, 621–629 (2011).
Google ScholarÂ
Lulli, M., Napoli, C., Landini, I., Mini, E. & Lapucci, A. Role of non-coding RNAs in colorectal cancer: focus on long non-coding RNAs. Int. J. Mol. Sci. 23, 13431 (2022).
Google ScholarÂ
Hu, G. et al. Molecular mechanisms of long noncoding RNAs and their role in disease pathogenesis. Oncotarget 9, 18648–18663 (2018).
Google ScholarÂ
Sebastian-delaCruz, M., Gonzalez-Moro, I., Olazagoitia-Garmendia, A., Castellanos-Rubio, A. & Santin, I. The role of lncRNAs in gene expression regulation through mRNA stabilization. Noncoding RNA 7, 3 (2021).
Google ScholarÂ
Tripathi, V. et al. The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol. Cell 39, 925–938 (2010).
Google ScholarÂ
Barbagallo, C. et al. LncRNA UCA1, upregulated in CRC biopsies and downregulated in serum exosomes, controls mRNA expression by RNA-RNA interactions. Mol. Ther. Nucleic Acids 12, 229–241 (2018).
Google ScholarÂ
Wang, L. et al. Long noncoding RNA (lncRNA)-mediated competing endogenous RNA networks provide novel potential biomarkers and therapeutic targets for colorectal cancer. Int. J. Mol. Sci. 20, 5758 (2019).
Google ScholarÂ
Xu, J., Xu, J., Liu, X. & Jiang, J. The role of lncRNA-mediated ceRNA regulatory networks in pancreatic cancer. Cell Death Discov. 8, 287 (2022).
Google ScholarÂ
Hu, J.-H., Tang, H.-N. & Wang, Y.-H. Cancer-associated fibroblast exosome LINC00355 promotes epithelial-mesenchymal transition and chemoresistance in colorectal cancer through the miR-34b-5p/CRKL axis. Cancer Gene Ther. 31, 259–272 (2024).
Google ScholarÂ
Chen, Z. et al. LncRNA SNHG16 drives PD-L1-mediated immune escape in colorectal cancer through regulating miR-324-3p/ELK4 signaling. Biochem. Genet. 63, 5496–5515 (2025).
Google ScholarÂ
Aznaourova, M. et al. Noncoding RNA MaIL1 is an integral component of the TLR4–TRIF pathway. Proc. Natl Acad. Sci. USA 117, 9042–9053 (2020).
Google ScholarÂ
Wang, X. et al. A novel LncRNA HITT forms a regulatory loop with HIF-1α to modulate angiogenesis and tumor growth. Cell Death Differ. 27, 1431–1446 (2020).
Google ScholarÂ
Semeradtova, A. et al. Extracellular vesicles in cancer’s communication: messages we can read and how to answer. Mol. Cancer 24, 86 (2025).
Google ScholarÂ
Welsh, J. A. et al. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J. Extracell. Vesicles 13, e12404 (2024).
Google ScholarÂ
Sun, R., He, X.-Y., Mei, C. & Ou, C.-L. Role of exosomal long non-coding RNAs in colorectal cancer. World J. Gastrointest. Oncol. 13, 867–878 (2021).
Google ScholarÂ
Ruiz-López, L. et al. The role of exosomes on colorectal cancer: a review. J. Gastroenterol. Hepatol. 33, 792–799 (2018).
Google ScholarÂ
van Niel, G., D’Angelo, G. & Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19, 213–228 (2018).
Google ScholarÂ
van Niel, G. et al. Challenges and directions in studying cell–cell communication by extracellular vesicles. Nat. Rev. Mol. Cell Biol. 23, 369–382 (2022).
Google ScholarÂ
Sun, J. et al. Tumor exosome promotes Th17 cell differentiation by transmitting the lncRNA CRNDE-h in colorectal cancer. Cell Death Dis. 12, 123 (2021).
Google ScholarÂ
Dixson, A. C., Dawson, T. R., Di Vizio, D. & Weaver, A. M. Context-specific regulation of extracellular vesicle biogenesis and cargo selection. Nat. Rev. Mol. Cell Biol. 24, 454–476 (2023).
Google ScholarÂ
Lu, Y. et al. Extracellular vesicles cargo orchestration in colorectal cancer: immune evasion, stromal remodeling, and therapeutic frontiers. Mol. Cancer 25, 10 (2025).
Google ScholarÂ
Wei, Z. et al. Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat. Commun. 8, 1145 (2017).
Google ScholarÂ
Jeppesen, D. K. et al. Reassessment of exosome composition. Cell 177, 428–445.e18 (2019).
Google ScholarÂ
O’Brien, K., Breyne, K., Ughetto, S., Laurent, L. C. & Breakefield, X. O. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat. Rev. Mol. Cell Biol. 21, 585–606 (2020).
Google ScholarÂ
O’Grady, T. et al. Sorting and packaging of RNA into extracellular vesicles shape intracellular transcript levels. BMC Biol. 20, 72 (2022).
Google ScholarÂ
Hinger, S. A. et al. Diverse long RNAs are differentially sorted into extracellular vesicles secreted by colorectal cancer cells. Cell Rep. 25, 715–725.e4 (2018).
Google ScholarÂ
Zhang, J. et al. LncRNA HLA-F-AS1 promotes colorectal cancer metastasis by inducing PFN1 in colorectal cancer-derived extracellular vesicles and mediating macrophage polarization. Cancer Gene Ther. 28, 1269–1284 (2021).
Google ScholarÂ
Zhao, J., Lin, H., Huang, K. & Li, S. Cancer-associated fibroblasts-derived extracellular vesicles carrying lncRNA SNHG3 facilitate colorectal cancer cell proliferation via the miR-34b-5p/HuR/HOXC6 axis. Cell Death Discov. 8, 346 (2022).
Google ScholarÂ
Yang, X., Li, Y., Zou, L. & Zhu, Z. Role of exosomes in crosstalk between cancer-associated fibroblasts and cancer cells. Front. Oncol. 9, 356 (2019).
Google ScholarÂ
Li, C., Teixeira, A. F., Zhu, H. J. & ten Dijke, P. Cancer associated-fibroblast-derived exosomes in cancer progression. Mol. Cancer 20, 154 (2021).
Google ScholarÂ
Zhou, L., Li, J., Tang, Y. & Yang, M. Exosomal LncRNA LINC00659 transferred from cancer-associated fibroblasts promotes colorectal cancer cell progression via miR-342-3p/ANXA2 axis. J. Transl. Med. 19, 8 (2021).
Google ScholarÂ
Chahal, S. et al. RNA on display: cell surface RNA as a novel layer of cellular regulation. Research 9, 1147 (2026).
Google ScholarÂ
Jiang, X. et al. Deciphering the RNA landscapes on mammalian cell surfaces. Protein Cell 17, 113–126 (2026).
Google ScholarÂ
Denaro, N., Merlano, M. C. & Lo Nigro, C. Long noncoding RNAs as regulators of cancer immunity. Mol. Oncol. 13, 61–73 (2019).
Google ScholarÂ
Luo, Y. et al. Long non-coding RNAs: emerging roles in the immunosuppressive tumor microenvironment. Front. Oncol. 10, 48 (2020).
Google ScholarÂ
Samadi, P., Shahnazari, M., Shekari, A., Maghool, F. & Jalali, A. A pan-cancer analysis indicates long noncoding RNA HAND2-AS1 as a potential prognostic, immunomodulatory and therapeutic biomarker in various cancers including colorectal adenocarcinoma. Cancer Cell Int. 23, 307 (2023).
Google ScholarÂ
Zhang, P., Cao, L., Zhou, R., Yang, X. & Wu, M. The lncRNA Neat1 promotes activation of inflammasomes in macrophages. Nat. Commun. 10, 1495 (2019).
Google ScholarÂ
Chen, Q., Qin, Y., Lin, M., Li, Z. & Tang, W. lncRNA NEAT1 promotes colorectal cancer progression by increasing inflammation. J. Oncol. 2022, 4088271 (2022).
Google ScholarÂ
Yin, S. et al. A novel ceRNA-immunoregulatory axis based on immune cell infiltration in ulcerative colitis-associated colorectal carcinoma by integrated weighted gene co-expression network analysis. BMC Gastroenterol. 22, 188 (2022).
Google ScholarÂ
Ye, D. et al. LncGMDS-AS1 promotes the tumorigenesis of colorectal cancer through HuR-STAT3/Wnt axis. Cell Death Dis. 14, 165 (2023).
Google ScholarÂ
Luo, Q. et al. LINC00460/miR-186-3p/MYC feedback loop facilitates colorectal cancer immune escape by enhancing CD47 and PD-L1 expressions. J. Exp. Clin. Cancer Res. 43, 225 (2024).
Google ScholarÂ
Han, B. et al. ELFN1-AS1 promotes GDF15-mediated immune escape of colorectal cancer from NK cells by facilitating GCN5 and SND1 association. Discov. Oncol. 14, 56 (2023).
Google ScholarÂ
Fang, H. et al. myCAF-derived exosomal PWAR6 accelerates CRC liver metastasis via altering glutamine availability and NK cell function in the tumor microenvironment. J. Hematol. Oncol. 17, 126 (2024).
Google ScholarÂ
Murray, P. J. Macrophage polarization. Annu. Rev. Physiol. 79, 541–566 (2017).
Google ScholarÂ
Mehla, K. & Singh, P. K. Metabolic regulation of macrophage polarization in cancer. Trends Cancer 5, 822–834 (2019).
Google ScholarÂ
Liang, Z. et al. LncRNA RPPH1 promotes colorectal cancer metastasis by interacting with TUBB3 and by promoting exosomes-mediated macrophage M2 polarization. Cell Death Dis. 10, 829 (2019).
Google ScholarÂ
Lai, F., Zhang, H., Xu, B., Xie, Y. & Yu, H. Long non-coding RNA NBR2 suppresses the progress of colorectal cancer in vitro and in vivo by regulating the polarization of TAM. Bioengineered 12, 5462–5475 (2021).
Google ScholarÂ
Yang, X. et al. Long non-coding RNA NBR2 suppresses the progression of colorectal cancer by downregulating miR-19a to regulate M2 macrophage polarization. Chin. J. Physiol. 66, 546–557 (2023).
Google ScholarÂ
Zhan, D. & Xian, H. Exploring the regulatory role of lncRNA in cancer immunity. Front. Oncol. 13, 1191913 (2023).
Google ScholarÂ
Wang, Y. et al. Regulatory roles of LncRNAs in colorectal cancer immune evasion: current concepts and future perspectives. Discov. Oncol. 16, 2064 (2025).
Google ScholarÂ
Lin, Z. et al. Long noncoding RNA KCNQ1OT1 is a prognostic biomarker and mediates CD8+ T cell exhaustion by regulating CD155 expression in colorectal cancer. Int. J. Biol. Sci. 17, 1757–1768 (2021).
Google ScholarÂ
Liu, J., Lv, W., Li, S. & Deng, J. Regulation of long non-coding RNA KCNQ1OT1 network in colorectal cancer immunity. Front. Genet. 12, 684002 (2021).
Google ScholarÂ
Xian, D., Niu, L., Zeng, J. & Wang, L. LncRNA KCNQ1OT1 secreted by tumor cell-derived exosomes mediates immune escape in colorectal cancer by regulating PD-L1 ubiquitination via miR-30a-5p/USP22. Front. Cell Dev. Biol. 9, 653808 (2021).
Google ScholarÂ
Yang, L. et al. VPS9D1-AS1 overexpression amplifies intratumoral TGF-β signaling and promotes tumor cell escape from CD8+ T cell killing in colorectal cancer. eLife 11, e79811 (2022). VPS9D1-AS1 overexpression amplifies intratumoural TGFβ signalling and promotes tumour cell escape from CD8+ T cell killing in colorectal cancer.
Google ScholarÂ
Xu, J. et al. MIR22HG acts as a tumor suppressor via TGFβ/SMAD signaling and facilitates immunotherapy in colorectal cancer. Mol. Cancer 19, 51 (2020).
Google ScholarÂ
Yu, H. et al. Long noncoding RNA MIR4435-2HG suppresses colorectal cancer initiation and progression by reprogramming neutrophils. Cancer Immunol. Res. 10, 1095–1110 (2022).
Google ScholarÂ
Gu, Y. et al. The lncRNA MIR181A1HG in extracellular vesicles derived from highly metastatic colorectal cancer cells promotes liver metastasis by remodeling the extracellular matrix and recruiting myeloid-derived suppressor cells. Cell Biosci. 15, 23 (2025).
Google ScholarÂ
Jin, K.-T., Yao, J.-Y., Fang, X.-L., Di, H. & Ma, Y.-Y. Roles of lncRNAs in cancer: focusing on angiogenesis. Life Sci. 252, 117647 (2020).
Google ScholarÂ
Mathonnet, M. et al. Hallmarks in colorectal cancer: angiogenesis and cancer stem-like cells. World J. Gastroenterol. 20, 4189–4196 (2014).
Google ScholarÂ
Nakasaki, T. et al. Expression of tissue factor and vascular endothelial growth factor is associated with angiogenesis in colorectal cancer. Am. J. Hematol. 69, 247–254 (2002).
Google ScholarÂ
Wu, H. et al. lncRNA PVT1 promotes tumorigenesis of colorectal cancer by stabilizing miR-16-5p and interacting with the VEGFA/VEGFR1/AKT axis. Mol. Ther. Nucleic Acids 20, 438–450 (2020).
Google ScholarÂ
Chen, X. et al. SP1-induced lncRNA-ZFAS1 contributes to colorectal cancer progression via the miR-150-5p/VEGFA axis. Cell Death Dis. 9, 982 (2018).
Google ScholarÂ
Wu, J. et al. Long non-coding RNA HNF1A-AS1 upregulates OTX1 to enhance angiogenesis in colon cancer via the binding of transcription factor PBX3. Exp. Cell Res. 393, 112025 (2020).
Google ScholarÂ
Zhang, L. et al. Induction of lncRNA NORAD accounts for hypoxia-induced chemoresistance and vasculogenic mimicry in colorectal cancer by sponging the miR-495-3p/ hypoxia-inducible factor-1α (HIF-1α). Bioengineered 13, 950–962 (2022).
Google ScholarÂ
Liu, J., Zhang, Q., Yang, D., Xie, F. & Wang, Z. The role of long non-coding RNAs in angiogenesis and anti-angiogenic therapy resistance in cancer. Mol. Ther. Nucleic Acids 28, 397–407 (2022).
Google ScholarÂ
Wang, F. W. et al. APC-activated long noncoding RNA inhibits colorectal carcinoma pathogenesis through reduction of exosome production. J. Clin. Investig. 129, 727–743 (2019).
Google ScholarÂ
Liu, S. et al. Ethoxy-erianin phosphate inhibits angiogenesis in colorectal cancer by regulating the TMPO-AS1/miR-126-3p/PIK3R2 axis and inactivating the PI3k/AKT signaling pathway. BMC Cancer 24, 1275 (2024).
Google ScholarÂ
Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16, 582–598 (2016).
Google ScholarÂ
Wang, M., Jiang, M., Xie, A., Zhang, N. & Xu, Y. Identification of CAF-related lncRNAs at the pan-cancer level represents a potential carcinogenic risk. Hum. Mol. Genet. 33, 1064–1073 (2024).
Google ScholarÂ
Hu, J. L. et al. CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol. Cancer 18, 91 (2019).
Google ScholarÂ
Li, F. et al. Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer. Transl. Oncol. 36, 101740 (2023).
Google ScholarÂ
Zhou, M., Wang, S., Liu, D. & Zhou, J. LINC01915 facilitates the conversion of normal fibroblasts into cancer-associated fibroblasts induced by colorectal cancer-derived extracellular vesicles through the miR-92a-3p/KLF4/CH25H axis. ACS Biomater. Sci. Eng. 7, 5255–5268 (2021).
Google ScholarÂ
Ren, J. et al. Carcinoma-associated fibroblasts promote the stemness and chemoresistance of colorectal cancer by transferring exosomal lncRNA H19. Theranostics 8, 3932–3948 (2018).
Google ScholarÂ
Zhu, S. et al. CAF-derived exosomal lncRNA FAL1 promotes chemoresistance to oxaliplatin by regulating autophagy in colorectal cancer. Dig. Liver Dis. 56, 330–342 (2024).
Google ScholarÂ
Radu, P. et al. The impact of cancer stem cells in colorectal cancer. Int. J. Mol. Sci. 25, 4140 (2024).
Google ScholarÂ
Huang, Y., Wang, L. & Liu, D. HOTAIR regulates colorectal cancer stem cell properties and promotes tumorigenicity by sponging miR-211-5p and modulating FLT-1. Cell Cycle 20, 1999–2009 (2021).
Google ScholarÂ
Crotti, S. et al. Extracellular matrix and colorectal cancer: how surrounding microenvironment affects cancer cell behavior? J. Cell. Physiol. 232, 967–975 (2017).
Google ScholarÂ
Le, C. C. et al. Functional interplay between collagen network and cell behavior within tumor microenvironment in colorectal cancer. Front. Oncol. 10, 527 (2020).
Google ScholarÂ
Vu, T. & Datta, P. K. Regulation of EMT in colorectal cancer: a culprit in metastasis. Cancers 9, 171 (2017).
Google ScholarÂ
Gugnoni, M. & Ciarrocchi, A. Long noncoding RNA and epithelial mesenchymal transition in cancer. Int. J. Mol. Sci. 20, 1924 (2019).
Google ScholarÂ
O’Brien, S. J. et al. Long non-coding RNA (lncRNA) and epithelial-mesenchymal transition (EMT) in colorectal cancer: a systematic review. Cancer Biol. Ther. 21, 769–781 (2020).
Google ScholarÂ
D’Angelo, E. & Agostini, M. Long non-coding RNA and extracellular matrix: the hidden players in cancer-stroma cross-talk. Noncoding RNA Res. 3, 174–177 (2018).
Google ScholarÂ
Heldin, C.-H., Vanlandewijck, M. & Moustakas, A. Regulation of EMT by TGFβ in cancer. FEBS Lett. 586, 1959–1970 (2012).
Google ScholarÂ
Wang, X. et al. LncRNA SNHG6 promotes proliferation, invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF1 and inducing EMT via regulation of ZEB1. Int. J. Med. Sci. 16, 51–59 (2019).
Google ScholarÂ
Kong, J. et al. Long non-coding RNA LINC01133 inhibits epithelial–mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6. Cancer Lett. 380, 476–484 (2016).
Google ScholarÂ
Wu, W. et al. Long noncoding RNA LINC01550 inhibits colorectal cancer malignancy by suppressing the Wnt/β-catenin signaling pathway. J. Biochem. Mol. Toxicol. 38, e23774 (2024).
Google ScholarÂ
Ye, H. et al. The SPI-induced long noncoding RNA, LINC00339, promotes tumorigenesis in colorectal cancer via the miR-378a-3p/MED19 axis. OncoTargets Ther. 13, 11711–11724 (2020).
Google ScholarÂ
Cui, Z. et al. Long non-coding RNA TTN-AS1 promotes the proliferation and invasion of colorectal cancer cells by activating mir-497-mediated PI3K/Akt/mTOR signaling. OncoTargets Ther. 12, 11531–11539 (2019).
Google ScholarÂ
Xu, J. et al. Long noncoding RNA DSCAM-AS1 facilitates colorectal cancer cell proliferation and migration via miR-137/Notch1 axis. J. Cancer 11, 6623–6632 (2020).
Google ScholarÂ
Wang, X. et al. The long non-coding RNA CYTOR drives colorectal cancer progression by interacting with NCL and Sam68. Mol. Cancer 17, 110 (2018).
Google ScholarÂ
Dastmalchi, N., Safaralizadeh, R. & Nargesi, M. M. LncRNAs: potential novel prognostic and diagnostic biomarkers in colorectal cancer. Curr. Med. Chem. 27, 5067–5077 (2020).
Google ScholarÂ
Badowski, C., He, B. & Garmire, L. X. Blood-derived lncRNAs as biomarkers for cancer diagnosis: the Good, the Bad and the Beauty. npj Precis. Oncol. 6, 40 (2022).
Google ScholarÂ
Zabeti Touchaei, A., Vahidi, S. & Samadani, A. A. Decoding the regulatory landscape of lncRNAs as potential diagnostic and prognostic biomarkers for gastric and colorectal cancers. Clin. Exp. Med. 24, 29 (2024).
Google ScholarÂ
Hu, D. et al. Plasma exosomal long non-coding RNAs serve as biomarkers for early detection of colorectal cancer. Cell. Physiol. Biochem. 51, 2704–2715 (2018).
Google ScholarÂ
Lin, Y. et al. Long non-coding RNAs as diagnostic and prognostic biomarkers for colorectal cancer (review). Oncol. Lett. 28, 486 (2024).
Google ScholarÂ
Zhao, Y. et al. Long noncoding RNA LINC02418 regulates MELK expression by acting as a ceRNA and may serve as a diagnostic marker for colorectal cancer. Cell Death Dis. 10, 568 (2019).
Google ScholarÂ
Liu, T. et al. Exosomal long noncoding RNA CRNDE-h as a novel serum-based biomarker for diagnosis and prognosis of colorectal cancer. Oncotarget 7, 85551–85563 (2016).
Google ScholarÂ
Fan, H., Zhu, J. & Yao, X. Long non-coding RNA PVT1 as a novel potential biomarker for predicting the prognosis of colorectal cancer. Int. J. Biol. Markers 33, 415–422 (2018).
Google ScholarÂ
Ozawa, T. et al. CCAT1 and CCAT2 long noncoding RNAs, located within the 8q.24.21 ‘gene desert’, serve as important prognostic biomarkers in colorectal cancer. Ann. Oncol. 28, 1882–1888 (2017).
Google ScholarÂ
Shen, X. et al. Circulating lncRNA DANCR as a potential auxillary biomarker for the diagnosis and prognostic prediction of colorectal cancer. Biosci. Rep. 40, BSR20191481 (2020).
Google ScholarÂ
WU, Z.-H. et al. Long non-coding RNA HOTAIR is a powerful predictor of metastasis and poor prognosis and is associated with epithelial-mesenchymal transition in colon cancer. Oncol. Rep. 32, 395–402 (2014).
Google ScholarÂ
Xu, W. et al. Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer. Int. J. Cancer 146, 2901–2912 (2020).
Google ScholarÂ
Zheng, H.-T. et al. High expression of lncRNA MALAT1 suggests a biomarker of poor prognosis in colorectal cancer. Int. J. Clin. Exp. Pathol. 7, 3174–3181 (2014).
Google ScholarÂ
Lu, Y. et al. lncRNA MIR100HG-derived miR-100 and miR-125b mediate cetuximab resistance via Wnt/β-catenin signaling. Nat. Med. 23, 1331–1341 (2017).
Google ScholarÂ
Liu, H. et al. Interaction of lncRNA MIR100HG with hnRNPA2B1 facilitates m6A-dependent stabilization of TCF7L2 mRNA and colorectal cancer progression. Mol. Cancer 21, 74 (2022).
Google ScholarÂ
Deng, X. et al. Long noncoding RNA CCAL transferred from fibroblasts by exosomes promotes chemoresistance of colorectal cancer cells. Int. J. Cancer 146, 1700–1716 (2020).
Google ScholarÂ
Yang, Y. et al. Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer. Cancer Cell Int. 18, 164 (2018).
Google ScholarÂ
Liu, Z. et al. Integrative analysis from multi-center studies identities a consensus machine learning-derived lncRNA signature for stage II/III colorectal cancer. eBioMedicine 75, 103750 (2022).
Google ScholarÂ
Schwarzmueller, L., Bril, O., Vermeulen, L. & Léveillé, N. Emerging role and therapeutic potential of lncRNAs in colorectal cancer. Cancers 12, 1–21 (2020).
Google ScholarÂ
Li, C. et al. Upregulated LINC01088 facilitates malignant phenotypes and immune escape of colorectal cancer by regulating microRNAs/G3BP1/PD-L1 axis. J. Cancer Res. Clin. Oncol. 148, 1965–1982 (2022).
Google ScholarÂ
Li, P. et al. MALAT1 is associated with poor response to oxaliplatin-based chemotherapy in colorectal cancer patients and promotes chemoresistance through EZH2. Mol. Cancer Ther. 16, 739–751 (2017).
Google ScholarÂ
Li, Z., Zhao, Z., Zhang, G., Liu, Y. & Zheng, S. LncRNA MEG3 inhibits the proliferation and migration abilities of colorectal cancer cells by competitively suppressing MiR-31 and reducing the binding of MiR-31 to target gene SFRP1. Aging 16, 2061–2076 (2023).
Google ScholarÂ
Coan, M., Haefliger, S., Ounzain, S. & Johnson, R. Targeting and engineering long non-coding RNAs for cancer therapy. Nat. Rev. Genet. 25, 578–595 (2024).
Google ScholarÂ
Paunovska, K., Loughrey, D. & Dahlman, J. E. Drug delivery systems for RNA therapeutics. Nat. Rev. Genet. 23, 265–280 (2022).
Google ScholarÂ
Pinkney, H. R., Ross, C. R., Hodgson, T. O., Pattison, S. T. & Diermeier, S. D. Discovery of prognostic lncRNAs in colorectal cancer using spatial transcriptomics. npj Precis. Oncol. 8, 230 (2024).
Google ScholarÂ
Hsu, C.-Y. et al. AI-driven multi-omics integration in precision oncology: bridging the data deluge to clinical decisions. Clin. Exp. Med. 26, 29 (2025).
Google ScholarÂ
Ding, A. X., Wang, H., Zhang, J. M., Yang, W. & Kuang, Y. T. lncRNA BANCR promotes the colorectal cancer metastasis through accelerating exosomes-mediated M2 macrophage polarization via regulating RhoA/ROCK signaling. Mol. Cell. Biochem. 479, 13–27 (2024).
Google ScholarÂ
Ma, D. et al. CCAT1 lncRNA promotes inflammatory bowel disease malignancy by destroying intestinal barrier via downregulating miR-185-3p. Inflamm. Bowel Dis. 25, 862–874 (2019).
Google ScholarÂ
Mao, D. et al. Long noncoding RNA GM16343 promotes IL-36β to regulate tumor microenvironment by CD8+ T cells. Technol. Cancer Res. Treat. 18, 1533033819883633 (2019).
Google ScholarÂ
Gao, C., Hu, W., Zhao, J., Ni, X. & Xu, Y. LncRNA HCG18 promotes M2 macrophage polarization to accelerate cetuximab resistance in colorectal cancer through regulating miR-365a-3p/FOXO1/CSF-1 axis. Pathol. Res. Pract. 240, 154227 (2022).
Google ScholarÂ
Zheng, J. et al. LINC00543 promotes colorectal cancer metastasis by driving EMT and inducing the M2 polarization of tumor associated macrophages. J. Transl. Med. 21, 153 (2023).
Google ScholarÂ
Wu, Q. et al. The establishment and experimental verification of an lncRNA-derived CD8+ T cell infiltration ceRNA network in colorectal cancer. Clin. Med. Insights Oncol. 16, 11795549221092218 (2022).
Google ScholarÂ
Tian, W. et al. MALAT1–miR663a negative feedback loop in colon cancer cell functions through direct miRNA–lncRNA binding. Cell Death Dis. 9, 857 (2018).
Google ScholarÂ
Zhou, L., Li, J., Liao, M., Zhang, Q. & Yang, M. LncRNA MIR155HG induces M2 macrophage polarization and drug resistance of colorectal cancer cells by regulating ANXA2. Cancer Immunol. Immunother. 71, 1075–1091 (2022).
Google ScholarÂ
Liu, R. et al. Inhibition of lncRNA NEAT1 suppresses the inflammatory response in IBD by modulating the intestinal epithelial barrier and by exosome-mediated polarization of macrophages. Int. J. Mol. Med. 42, 2903–2913 (2018).
Google ScholarÂ
Zhang, M. et al. Knockdown of NEAT1 induces tolerogenic phenotype in dendritic cells by inhibiting activation of NLRP3 inflammasome. Theranostics 9, 3425–3442 (2019).
Google ScholarÂ
Li, J. S., Liu, T. M., Li, L. & Jiang, C. LncRNA PROX1 antisense RNA 1 promotes PD-L1-mediated proliferation, metastasis, and immune escape in colorectal cancer by interacting with miR-520d. Anticancer Drugs 34, 669–679 (2023).
Google ScholarÂ
Wang, Y. et al. Hypoxia-induced PTTG3P contributes to colorectal cancer glycolysis and M2 phenotype of macrophage. Biosci. Rep. 41, BSR20210764 (2021).
Google ScholarÂ
Huang, Y. et al. Exosomal lncRNA SNHG10 derived from colorectal cancer cells suppresses natural killer cell cytotoxicity by upregulating INHBC. Cancer Cell Int. 21, 528 (2021).
Google ScholarÂ
Zhou, N. et al. LncRNA SNHG4 promotes malignant biological behaviors and immune escape of colorectal cancer cells by regulating the miR-144-3p/MET axis. Am. J. Transl. Res. 13, 11144–11161 (2021).
Google ScholarÂ
Gao, B. et al. Colon cancer-derived exosomal lncRNA-XIST promotes M2-like macrophage polarization by regulating PDGFRA. Int. J. Mol. Sci. 25, 11433 (2024).
Google ScholarÂ
Ruan, L., Chen, W., Zhao, X., Fang, N. & Li, T. Predictive potentials of ZEB1-AS1 in colorectal cancer prognosis and their correlation with immunotherapy. J. Oncol. 2022, 1084555 (2022).
Google ScholarÂ
Gu, Y., Wang, G. & Xu, H. Long non-coding RNA ZNFX1 antisense 1 (ZFAS1) suppresses anti-oxidative stress in chondrocytes during osteoarthritis by sponging microRNA-1323. Bioengineered 13, 13188–13200 (2022).
Google ScholarÂ
Huang, S. et al. SOX2 promotes vasculogenic mimicry by accelerating glycolysis via the lncRNA AC005392.2-GLUT1 axis in colorectal cancer. Cell Death Dis. 14, 791 (2023).
Google ScholarÂ
Zheng, S. et al. Long non-coding RNA AK001058 regulates tumor growth and angiogenesis in colorectal cancer via methylation of ADAMTS12. Am. J. Transl. Res. 11, 6117–6123 (2019).
Google ScholarÂ
Gu, C. et al. Long non-coding RNA CCAT1 promotes colorectal cancer cell migration, invasiveness and viability by upregulating VEGF via negative modulation of microRNA-218. Exp. Ther. Med. 19, 2543–2550 (2020).
Google ScholarÂ
Zhou, J. et al. Facilitating colorectal cancer cell metastasis by targeted binding of long non-coding RNA ENSG00000231881 with miR-133b via VEGFC signaling pathway. Biochem. Biophys. Res. Commun. 509, 1–7 (2019).
Google ScholarÂ
Pichler, M. et al. Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer. Gut 69, 1818–1831 (2020).
Google ScholarÂ
Song, J., Shu, H., Zhang, L. & Xiong, J. Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β-catenin signaling pathway. J. Cell. Biochem. 120, 6937–6951 (2019).
Google ScholarÂ
Xu, X. et al. LINC00337 promotes tumor angiogenesis in colorectal cancer by recruiting DNMT1, which suppresses the expression of CNN1. Cancer Gene Ther. 28, 1285–1297 (2021).
Google ScholarÂ
Chang, L. et al. Long intergenic non-protein-coding RNA 467 promotes tumor progression and angiogenesis via the microRNA-128-3p/vascular endothelial growth factor C axis in colorectal cancer. Bioengineered 13, 12392–12408 (2022).
Google ScholarÂ
Zhang, G. et al. METTL3 dual regulation of the stability of LINC00662 and VEGFA RNAs promotes colorectal cancer angiogenesis. Discov. Oncol. 13, 89 (2022).
Google ScholarÂ
Xu, T. et al. Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4α and WNK2 regulation. Cell. Oncol. 43, 297–310 (2020).
Google ScholarÂ
Liang, W., Wu, J. & Qiu, X. LINC01116 facilitates colorectal cancer cell proliferation and angiogenesis through targeting EZH2-regulated TPM1. J. Transl. Med. 19, 45 (2021).
Google ScholarÂ
Yuan, Y. & Long, Z. LncRNA LINC01232 enhances proliferation, angiogenesis, migration and invasion of colon adenocarcinoma cells by downregulating miR-181a-5p. J. Microbiol. Biotechnol. 33, 398–409 (2023).
Google ScholarÂ
Xu, S. et al. STAT2-induced linc02231 promotes tumorigenesis and angiogenesis through modulation of hnRNPA1/ANGPTL4 in colorectal cancer. J. Gene Med. 25, e3506 (2023).
Google ScholarÂ
Chang, L. et al. A novel lncRNA LOC101928222 promotes colorectal cancer angiogenesis by stabilizing HMGCS2 mRNA and increasing cholesterol synthesis. J. Exp. Clin. Cancer Res. 43, 185 (2024).
Google ScholarÂ
Guo, T., Liu, D., Peng, S., Wang, M. & Li, Y. A positive feedback loop of lncRNA MIR31HG-miR-361-3p -YY1 accelerates colorectal cancer progression through modulating proliferation, angiogenesis, and glycolysis. Front. Oncol. 11, 684984 (2021).
Google ScholarÂ
Liu, H., Li, A., Sun, Z., Zhang, J. & Xu, H. Long non-coding RNA NEAT1 promotes colorectal cancer progression by regulating miR-205-5p/VEGFA axis. Hum. Cell 33, 386–396 (2020).
Google ScholarÂ
Dong, H., Liu, Q., Chen, C., Lu, T. & Xu, K. LncRNA OGFRP1 promotes angiogenesis and epithelial-mesenchymal transition in colorectal cancer cells through miR-423-5p/CTCF axis. Immunobiology 227, 152176 (2022).
Google ScholarÂ
Liu, Y. et al. SNHG17 promotes the proliferation and migration of colorectal adenocarcinoma cells by modulating CXCL12-mediated angiogenesis. Cancer Cell Int. 20, 566 (2020).
Google ScholarÂ
Zhang, L.-M., Wang, P., Liu, X.-M. & Zhang, Y.-J. LncRNA SUMO1P3 drives colon cancer growth, metastasis and angiogenesis. Am. J. Transl. Res. 9, 5461–5472 (2017).
Google ScholarÂ
Zhang, Y. et al. Long non-coding RNA TPT1-AS1 promotes angiogenesis and metastasis of colorectal cancer through TPT1-AS1/NF90/VEGFA signaling pathway. Aging 12, 6191–6205 (2020).
Google ScholarÂ
