Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Lncrna CASC15 Activated By TCF12 Promote Colorectal Cancer Progression via EMT

Author(s): Shuai Yan, Ming Yuan, Xichen Yang, Xianting Huang, Dan Wu, Nanyao Wang, Xia Sun, Ya Qin, Yanhua Fei, Zhenguo Zhao* and Qiong Wang*

Volume 27, Issue 8, 2024

Published on: 15 September, 2023

Page: [1222 - 1230] Pages: 9

DOI: 10.2174/1386207326666230901120611

Price: $65

conference banner
Abstract

Background: Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors.

Objective: Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC.

Methods: Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT).

Results: We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression.

Conclusion: Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.

Keywords: CRC, CASC15, TCF12, EMT, proliferation, migration.

Graphical Abstract
[1]
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin., 2021, 71(1), 7-33.
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[2]
Rychahou, P.; Bae, Y.; Reichel, D.; Zaytseva, Y.Y.; Lee, E.Y.; Napier, D.; Weiss, H.L.; Roller, N.; Frohman, H.; Le, A.T.; Mark Evers, B. Colorectal cancer lung metastasis treatment with polymer–drug nanoparticles. J. Control. Release, 2018, 275, 85-91.
[http://dx.doi.org/10.1016/j.jconrel.2018.02.008] [PMID: 29421609]
[3]
Harada, S.; Morlote, D. Molecular pathology of colorectal cancer. Adv. Anat. Pathol., 2020, 27(1), 20-26.
[http://dx.doi.org/10.1097/PAP.0000000000000247] [PMID: 31503031]
[4]
Nagano, T.; Fraser, P. No-nonsense functions for long noncoding RNAs. Cell, 2011, 145(2), 178-181.
[http://dx.doi.org/10.1016/j.cell.2011.03.014] [PMID: 21496640]
[5]
Peng, W-X.; Koirala, P.; Mo, Y.Y. LncRNA-mediated regulation of cell signaling in cancer. Oncogene, 2017, 36(41), 5661-5667.
[http://dx.doi.org/10.1038/onc.2017.184] [PMID: 28604750]
[6]
Ali, T.; Grote, P. Beyond the RNA-dependent function of LncRNA genes. eLife, 2020, 9, e60583.
[http://dx.doi.org/10.7554/eLife.60583] [PMID: 33095159]
[7]
Ghafouri-Fard, S.; Hussen, B.M.; Gharebaghi, A.; Eghtedarian, R.; Taheri, M. LncRNA signature in colorectal cancer. Pathol. Res. Pract., 2021, 222, 153432.
[http://dx.doi.org/10.1016/j.prp.2021.153432] [PMID: 33857856]
[8]
Xu, M.; Chen, X.; Lin, K.; Zeng, K.; Liu, X.; Xu, X.; Pan, B.; Xu, T.; Sun, L.; He, B.; Pan, Y.; Sun, H.; Wang, S. lncRNA SNHG6 regulates EZH2 expression by sponging miR-26a/b and miR-214 in colorectal cancer. J. Hematol. Oncol., 2019, 12(1), 3.
[http://dx.doi.org/10.1186/s13045-018-0690-5] [PMID: 30626446]
[9]
Ni, W.; Yao, S.; Zhou, Y.; Liu, Y.; Huang, P.; Zhou, A.; Liu, J.; Che, L.; Li, J. Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3. Mol. Cancer, 2019, 18(1), 143.
[http://dx.doi.org/10.1186/s12943-019-1079-y] [PMID: 31619268]
[10]
Gu, X.; Chu, Q.; Zheng, Q.; Wang, J.; Zhu, H. The dual functions of the long noncoding RNA CASC15 in malignancy. Biomed. Pharmacother., 2021, 135, 111212.
[http://dx.doi.org/10.1016/j.biopha.2020.111212] [PMID: 33433353]
[11]
Wu, Q.; Xiang, S.; Ma, J.; Hui, P.; Wang, T.; Meng, W.; Shi, M.; Wang, Y. Long non‐coding RNA CASC 15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN 1A and ZEB 1. Mol. Oncol., 2018, 12(6), 799-813.
[http://dx.doi.org/10.1002/1878-0261.12187] [PMID: 29489064]
[12]
Yao, X.M.; Tang, J.H.; Zhu, H.; Jing, Y. High expression of LncRNA CASC15 is a risk factor for gastric cancer prognosis and promote the proliferation of gastric cancer. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(24), 5661-5667.
[PMID: 29272000]
[13]
Liang, C.; Wang, J.; Liu, A.; Wu, Y. Tumor promoting long non‐coding RNA CASC15 affects HMGB2 expression by sponging miR‐582‐5p in colorectal cancer. J. Gene Med., 2022, 24(6), e3308.
[http://dx.doi.org/10.1002/jgm.3308] [PMID: 33395735]
[14]
Yang, J.; Zhang, L.; Jiang, Z.; Ge, C.; Zhao, F.; Jiang, J.; Tian, H.; Chen, T.; Xie, H.; Cui, Y.; Yao, M.; Li, H.; Li, J. TCF12 promotes the tumorigenesis and metastasis of hepatocellular carcinoma via upregulation of CXCR4 expression. Theranostics, 2019, 9(20), 5810-5827.
[http://dx.doi.org/10.7150/thno.34973] [PMID: 31534521]
[15]
Wang, B.; Xu, W.; Cai, Y.; Guo, C.; Zhou, G.; Yuan, C. CASC15: A tumor-associated long non-coding RNA. Curr. Pharm. Des., 2021, 27(1), 127-134.
[http://dx.doi.org/10.2174/1381612826666200922153701] [PMID: 32962611]
[16]
Li, Y.; Chen, G.; Yan, Y.; Fan, Q. CASC15 promotes epithelial to mesenchymal transition and facilitates malignancy of hepatocellular carcinoma cells by increasing TWIST1 gene expression via miR-33a-5p sponging. Eur. J. Pharmacol., 2019, 860, 172589.
[http://dx.doi.org/10.1016/j.ejphar.2019.172589] [PMID: 31401158]
[17]
Bai, Y.; Zhang, G.; Cheng, R.; Yang, R.; Chu, H. CASC15 contributes to proliferation and invasion through regulating miR-766-5p/ KLK12 axis in lung cancer. Cell Cycle, 2019, 18(18), 2323-2331.
[http://dx.doi.org/10.1080/15384101.2019.1646562] [PMID: 31378128]
[18]
Gao, R.; Fang, C.; Xu, J.; Tan, H.; Li, P.; Ma, L. LncRNA CACS15 contributes to oxaliplatin resistance in colorectal cancer by positively regulating ABCC1 through sponging miR-145. Arch. Biochem. Biophys., 2019, 663, 183-191.
[http://dx.doi.org/10.1016/j.abb.2019.01.005] [PMID: 30639170]
[19]
Zheng, K.; Xie, H.; Wu, W.; Wen, X.; Zeng, Z.; Shi, Y. CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p. Cancer Cell Int., 2021, 21(1), 27.
[http://dx.doi.org/10.1186/s12935-020-01699-6] [PMID: 33413401]
[20]
Gao, S.; Bian, T.; Zhang, Y.; Su, M.; Liu, Y. TCF12 overexpression as a poor prognostic factor in ovarian cancer. Pathol. Res. Pract., 2019, 215(9), 152527.
[http://dx.doi.org/10.1016/j.prp.2019.152527] [PMID: 31311684]
[21]
Gao, S.; Bian, T.; Su, M.; Liu, Y.; Zhang, Y. miR-26a inhibits ovarian cancer cell proliferation, migration and invasion by targeting TCF12. Oncol. Rep., 2020, 43(1), 368-374.
[PMID: 31789414]
[22]
Lee, C.C.; Chen, W.S.; Chen, C.C.; Chen, L.L.; Lin, Y.S.; Fan, C.S.; Huang, T.S. TCF12 protein functions as transcriptional repressor of E-cadherin, and its overexpression is correlated with metastasis of colorectal cancer. J. Biol. Chem., 2012, 287(4), 2798-2809.
[http://dx.doi.org/10.1074/jbc.M111.258947] [PMID: 22130667]
[23]
Goossens, S.; Vandamme, N.; Van Vlierberghe, P.; Berx, G. EMT transcription factors in cancer development re-evaluated: Beyond EMT and MET. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(2), 584-591.
[http://dx.doi.org/10.1016/j.bbcan.2017.06.006] [PMID: 28669750]
[24]
Brabletz, S.; Schuhwerk, H.; Brabletz, T.; Stemmler, M.P. Dynamic EMT: A multi‐tool for tumor progression. EMBO J., 2021, 40(18), e108647.
[http://dx.doi.org/10.15252/embj.2021108647] [PMID: 34459003]
[25]
Vu, T.; Datta, P. Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers., 2017, 9(12), 171.
[http://dx.doi.org/10.3390/cancers9120171] [PMID: 29258163]
[26]
Wang, X.; Wang, J.; Wu, J. Emerging roles for HMGA2 in colorectal cancer. Transl. Oncol., 2021, 14(1), 100894.
[http://dx.doi.org/10.1016/j.tranon.2020.100894] [PMID: 33069103]
[27]
Wang, T.; Lin, F.; Sun, X.; Jiang, L.; Mao, R.; Zhou, S.; Shang, W.; Bi, R.; Lu, F.; Li, S. HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation. Cancer Cell Int., 2019, 19(1), 3.
[http://dx.doi.org/10.1186/s12935-018-0717-6] [PMID: 30622439]
[28]
Zhang, C LncRNA CASC21 induces HGH1 to mediate colorectal cancer cell proliferation, migration, EMT and stemness. RNA Biol., 2021, 18(S1), 369-381.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy