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Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p

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Pathology & Oncology Research

Abstract

Colorectal cancer remains one of most common cancer types with poor prognosis globally. Recent years, numerous studies depicted pivotal roles of lncRNAs in colorectal cancer progression. This study aimed to investigate the role of FGF14-AS2 in colorectal cancer development. FGF14-AS2 was found as a significantly downregulated lncRNA in TCGA dataset. Via RT-qPCR, we confirmed the downregulation of FGF14-AS2 in collected colorectal carcinoma samples. Transfection of plasmid containing full length of FGF14-AS2 repressed cell proliferation and induced elevation of cell apoptosis in colorectal cancer cells. In addition, FGF14-AS2 overexpression inactivated MAPK/ERK signaling in cells. Bioinformatic analysis and subsequent cell-based assays showed that FGF14-AS2 sponging miR-1288-3p, an oncogenic miRNA in colorectal cancer. RERG, the regulator of Ras/ERK pathway, was predicted and verified as target gene of miR-1288. Via downregulation of miR-1288, FGF14-AS2 elevated RERG expression in colorectal cancer cells. Rescue assays indicated that FGF14-AS2 relied on regulation of RERG to control cell proliferation and apoptosis in colorectal cancer. Taken together, the current study demonstrated FGF14-AS2 as a regulator of colorectal cancer development via downregulation of miR-1288-3p and inactivation of Ras/ERK signaling.

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References

  1. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69:7–34

    PubMed  Google Scholar 

  2. Rosello S, Papaccio F, Roda D, Tarazona N, Cervantes A (2018) The role of chemotherapy in localized and locally advanced rectal cancer: a systematic revision. Cancer Treat Rev 63:156–171

    Article  CAS  Google Scholar 

  3. Mitra SA, Mitra AP, Triche TJ (2012) A central role for long non-coding RNA in cancer. Front Genet 3:17

    Article  CAS  Google Scholar 

  4. Fan Q, Liu B (2018) Comprehensive analysis of a long noncoding RNA-associated competing endogenous RNA network in colorectal cancer. Onco Targets Ther 11:2453–2466

    Article  Google Scholar 

  5. Wei L, Wang X, Lv L, Zheng Y, Zhang N, Yang M (2019) The emerging role of noncoding RNAs in colorectal cancer chemoresistance. Cell Oncol (Dordr) 42:757–768

    Article  CAS  Google Scholar 

  6. Xu T, Wu K, Zhang L, et al. (2019) Long non-coding RNA LINC00858 exerts a tumor-promoting role in colon cancer via HNF4alpha and WNK2 regulation. Cell Oncol (Dordr)

  7. Bhan A, Mandal SS (2014) Long noncoding RNAs: emerging stars in gene regulation, epigenetics and human disease. ChemMedChem. 9:1932–1956

    Article  CAS  Google Scholar 

  8. Xu Y, Zhang X, Hu X, Zhou W, Zhang P, Zhang J, Yang S, Liu Y (2018) The effects of lncRNA MALAT1 on proliferation, invasion and migration in colorectal cancer through regulating SOX9. Mol Med 24:52

    Article  Google Scholar 

  9. Yang F, Liu YH, Dong SY, Ma RM, Bhandari A, Zhang XH, Wang OC (2016) A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer. Biochem Biophys Res Commun 470:479–483

    Article  CAS  Google Scholar 

  10. Yang Y, Xun N, Wu JG (2019) Long non-coding RNA FGF14-AS2 represses proliferation, migration, invasion, and induces apoptosis in breast cancer by sponging miR-205-5p. Eur Rev Med Pharmacol Sci 23:6971–6982

    CAS  PubMed  Google Scholar 

  11. Burotto M, Chiou VL, Lee JM, Kohn EC (2014) The MAPK pathway across different malignancies: a new perspective. Cancer. 120:3446–3456

    Article  CAS  Google Scholar 

  12. Sun QY, Ding LW, Johnson K, Zhou S, Tyner JW, Yang H, Doan NB, Said JW, Xiao JF, Loh XY, Ran XB, Venkatachalam N, Lao Z, Chen Y, Xu L, Fan LF, Chien W, Lin DC, Koeffler HP (2019) SOX7 regulates MAPK/ERK-BIM mediated apoptosis in cancer cells. Oncogene. 38:6196–6210

    Article  CAS  Google Scholar 

  13. Pan H, Wang Y, Na K, Wang Y, Wang L, Li Z, Guo C, Guo D, Wang X (2019) Autophagic flux disruption contributes to Ganoderma lucidum polysaccharide-induced apoptosis in human colorectal cancer cells via MAPK/ERK activation. Cell Death Dis 10:456

    Article  Google Scholar 

  14. Zhang X, Ma L, Qi J, Shan H, Yu W, Gu Y (2015)MAPK/ERK signaling pathway-inducedhyper-O-GlcNAcylation enhances cancer malignancy. Mol Cell Biochem 410:101–110

    Article  CAS  Google Scholar 

  15. Finlin BS, Gau CL, Murphy GA, Shao H, Kimel T, Seitz RS, Chiu YF, Botstein D, Brown PO, der CJ, Tamanoi F, Andres DA, Perou CM (2001) RERG is a novel ras-related, estrogen-regulated and growth-inhibitory gene in breast cancer. J Biol Chem 276:42259–42267

    Article  CAS  Google Scholar 

  16. Habashy HO, Powe DG, Glaab E, Ball G, Spiteri I, Krasnogor N, Garibaldi JM, Rakha EA, Green AR, Caldas C, Ellis IO (2011) RERG (Ras-like, oestrogen-regulated, growth-inhibitor) expression in breast cancer: a marker of ER-positive luminal-like subtype. Breast Cancer Res Treat 128:315–326

    Article  CAS  Google Scholar 

  17. Wang AG, Fang W, Han YH, Cho SM, Choi JY, Lee KH, Kim WH, Kim JM, Park MG, Yu DY, Kim NS, Lee DS (2006) Expression of the RERG gene is gender-dependent in hepatocellular carcinoma and regulated by histone deacetyltransferases. J Korean Med Sci 21:891–896

    Article  CAS  Google Scholar 

  18. Xiong Y, Huang H, Chen S, Dai H, Zhang L (2019) ERK5regulated RERG expression promotes cancer progression in prostatic carcinoma. Oncol Rep 41:1160–1168

    CAS  PubMed  Google Scholar 

  19. Yang R, Chen B, Pfutze K, Buch S, Steinke V, Holinski-Feder E, Stocker S, von Schonfels W, Becker T, Schackert HK, Royer-Pokora B, Kloor M, Schmiegel WH, Buttner R, Engel C, Lascorz Puertolas J, Forsti A, Kunkel N, Bugert P, Schreiber S, Krawczak M, Schafmayer C, Propping P, Hampe J, Hemminki K, Burwinkel B (2014)Genome-wide analysis associates familial colorectal cancer with increases in copy number variations and a rare structural variation at 12p12.3. Carcinogenesis. 35:315–323

    Article  CAS  Google Scholar 

  20. Chen Y, Yu X, Xu Y, Shen H (2017) Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis. Cancer Med 6:2321–2330

    Article  CAS  Google Scholar 

  21. Berg M, Soreide K (2012) EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways in colorectal cancer: implications for targeted therapy. Discov Med 14:207–214

    PubMed  Google Scholar 

  22. Berg M, Danielsen SA, Ahlquist T, Merok MA, Ågesen TH, Vatn MH, Mala T, Sjo OH, Bakka A, Moberg I, Fetveit T, Mathisen Ø, Husby A, Sandvik O, Nesbakken A, Thiis-Evensen E, Lothe RA (2010) DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset. PLoS One 5:e13978

    Article  Google Scholar 

  23. Wang Q, Yang L, Hu X, Jiang Y, Hu Y, Liu Z, Liu J, Wen T, Ma Y, An G, Feng G (2017) Upregulated NNT-AS1, a long noncoding RNA, contributes to proliferation and migration of colorectal cancer cells in vitro and in vivo. Oncotarget. 8:3441–3453

    Article  Google Scholar 

  24. Sang B, Zhang YY, Guo ST, Kong LF, Cheng Q, Liu GZ, Thorne RF, Zhang XD, Jin L, Wu M (2018) Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence. Proc Natl Acad Sci U S A 115:E11661–E11E70

    Article  CAS  Google Scholar 

  25. Zhao W, Ma N, Wang S, Mo Y, Zhang Z, Huang G, Midorikawa K, Hiraku Y, Oikawa S, Murata M, Takeuchi K (2017) RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-kappaB signaling pathway in nasopharyngeal carcinoma. J Exp Clin Cancer Res 36:88

    Article  Google Scholar 

  26. Ho JY, Hsu RJ, Liu JM, Chen SC, Liao GS, Gao HW, Yu CP (2017)MicroRNA-382-5p aggravates breast cancer progression by regulating the RERG/Ras/ERK signaling axis. Oncotarget. 8:22443–22459

    Article  Google Scholar 

  27. Zhang Y, Ren S, Yuan F et al (2018)miR-135 promotes proliferation and stemness of oesophageal squamous cell carcinoma by targeting RERG. Artif Cells Nanomed Biotechnol 46:1210–1219

    Article  CAS  Google Scholar 

  28. Gopalan V, Pillai S, Ebrahimi F, Salajegheh A, Lam TC, le TK, Langsford N, Ho YH, Smith RA, Lam AKY (2014) Regulation of microRNA-1288 in colorectal cancer: altered expression and its clinicopathological significance. Mol Carcinog 53(Suppl 1):E36–E44

    Article  CAS  Google Scholar 

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Ruizhi Hou, Yan Liu, Yanzhuo Su, Zhenbo Shu acquired data and performed data analysis. Ruizhi Hou and Yan Liu designed the study. Yanzhuo Su and Zhenbo Shu wrote the manuscript. Study was supervised by Zhenbo Shu.

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Correspondence to Zhenbo Shu.

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The study was performed in accordance with the Declaration of Helsinki and obtained the approval from ethical approval board of the Third Hospital of Jilin University.

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Hou, R., Liu, Y., Su, Y. et al. Overexpression of Long Non-Coding RNA FGF14-AS2 Inhibits Colorectal Cancer Proliferation Via the RERG/Ras/ERK Signaling by Sponging microRNA-1288-3p. Pathol. Oncol. Res. 26, 2659–2667 (2020). https://doi.org/10.1007/s12253-020-00862-8

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