lncRNA FLVCR1‑AS1 drives colorectal cancer progression via modulation of the miR‑381/RAP2A axis

Han,Yi; Wang,Xiaoyan; Mao,Enqiang; Shen,Boyong; Huang,Liang

doi:10.3892/mmr.2020.11778

lncRNA FLVCR1‑AS1 drives colorectal cancer progression via modulation of the miR‑381/RAP2A axis

Authors:
- Yi Han
- Xiaoyan Wang
- Enqiang Mao
- Boyong Shen
- Liang Huang
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Affiliations: Department of Traumatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, P.R. China, Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, P.R. China
Published online on: December 13, 2020 https://doi.org/10.3892/mmr.2020.11778
Article Number: 139
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the most prevalent types of cancer globally. Long non‑coding RNAs (lncRNAs) have been suggested to serve as vital regulators in CRC. lncRNA feline leukemia virus subgroup C receptor 1 antisense RNA 1 (FLVCR1‑AS1) is closely associated with the tumorigenesis of various types of cancer. The aim of the present study was to investigate the molecular mechanisms of lncRNA FLVCR1‑AS1 in CRC progression. The expression levels of FLVCR1‑AS1, microRNA (miR)‑381 and Ras‑related protein 2a (RAP2A) were measured by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A Kaplan‑Meier analysis was performed to determine the overall survival rate of patients with CRC. Furthermore, cell viability, migration and invasion were assessed using Cell Counting Kit‑8 (CCK‑8) and Transwell assays. The interaction between genes was confirmed using dual‑luciferase reporter and pull‑down assays. The results demonstrated that FLVCR1‑AS1 was upregulated in CRC tissues and cells, and increased FLVCR1‑AS1 expression levels in patients with CRC were associated with poor prognosis. FLVCR1‑AS1 knockdown significantly attenuated the viability, migration and invasion ability of CRC cells. In addition, the results confirmed that FLVCR1‑AS1 directly binds with miR‑381‑3p, and that RAP2A is a direct target of miR‑381‑3p. The overexpression of FLVCR1‑AS1 increased RAP2A expression levels. Functional assays revealed that miR‑381 inhibitor or RAP2A overexpression attenuated the suppressive effects of FLVCR1‑AS1 silencing on CRC cell viability, migration and invasion. Overall, the findings of the current study suggest that FLVCR1‑AS1 promotes CRC progression via the miR‑381/RAP2A pathway. These findings may provide a novel approach for CRC treatment.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2019. CA Cancer J Clin. 69:7–34. 2019. View Article : Google Scholar : PubMed/NCBI
2	Ahnen DJ, Wade SW, Jones WF, Sifri R, Mendoza Silveiras J, Greenamyer J, Guiffre S, Axilbund J, Spiegel A and You YN: The increasing incidence of young-onset colorectal cancer: A call to action. Mayo Clin Proc. 89:216–224. 2014. View Article : Google Scholar : PubMed/NCBI
3	Ladabaum U, Dominitz JA, Kahi C and Schoen RE: Strategies for colorectal cancer screening. Gastroenterology. 158:418–432. 2020. View Article : Google Scholar : PubMed/NCBI
4	Uszczynska-Ratajczak B, Lagarde J, Frankish A, Guigó R and Johnson R: Towards a complete map of the human long non-coding RNA transcriptome. Nat Rev Genet. 19:535–548. 2018. View Article : Google Scholar : PubMed/NCBI
5	Davalos V and Esteller M: Disruption of long noncoding RNAs targets cancer hallmark pathways in lung tumorigenesis. Cancer Res. 79:3028–3030. 2019. View Article : Google Scholar : PubMed/NCBI
6	Wu F, Sui Y, Wang Y, Xu T, Fan L and Zhu H: Long noncoding RNA SNHG7, a molecular sponge for microRNA-485, promotes the aggressive behavior of cervical cancer by regulating PAK4. Onco Targets Ther. 13:685–699. 2020. View Article : Google Scholar : PubMed/NCBI
7	Zhang S, Ding L, Gao F and Fan H: Long non-coding RNA DSCAM-AS1 upregulates USP47 expression through sponging miR-101-3p to accelerate osteosarcoma progression. Biochem Cell Biol. 98:600–611. 2020. View Article : Google Scholar : PubMed/NCBI
8	Wang R, Huang Z, Qian C, Wang M, Zheng Y, Jiang R and Yu C: LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis. Biochem Biophys Res Commun. 526:1005–1012. 2020. View Article : Google Scholar : PubMed/NCBI
9	Fang Y, Zhang S, Yin J, Shen YX, Wang H, Chen XS and Tang H: LINC01535 promotes proliferation and inhibits apoptosis in esophageal squamous cell cancer by activating the JAK/STAT3 pathway. Eur Rev Med Pharmacol Sci. 24:3694–3700. 2020.PubMed/NCBI
10	Yan Z, Zhang W, Xiong Y, Wang Y and Li Z: Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis. Biochem Biophys Res Commun. 521:716–720. 2020. View Article : Google Scholar : PubMed/NCBI
11	Yan H, Li H, Silva MA, Guan Y, Yang L, Zhu L, Zhang Z, Li G and Ren C: LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer. J Exp Clin Cancer Res. 38:3562019. View Article : Google Scholar : PubMed/NCBI
12	Lin H, Shangguan Z, Zhu M, Bao L, Zhang Q and Pan S: lncRNA FLVCR1-AS1 silencing inhibits lung cancer cell proliferation, migration, and invasion by inhibiting the activity of the Wnt/β-catenin signaling pathway. J Cell Biochem. 120:10625–10632. 2019. View Article : Google Scholar : PubMed/NCBI
13	Luo H, Xu C, Le W, Ge B and Wang T: lncRNA CASC11 promotes cancer cell proliferation in bladder cancer through miRNA-150. J Cell Biochem. 120:13487–13493. 2019. View Article : Google Scholar : PubMed/NCBI
14	Peng CL, Zhao XJ, Wei CC and Wu JW: LncRNA HOTAIR promotes colon cancer development by down-regulating miRNA-34a. Eur Rev Med Pharmacol Sci. 23:5752–5761. 2019.PubMed/NCBI
15	Lai XJ and Cheng HF: LncRNA colon cancer-associated transcript 1 (CCAT1) promotes proliferation and metastasis of ovarian cancer via miR-1290. Eur Rev Med Pharmacol Sci. 22:322–328. 2018.PubMed/NCBI
16	Wang C, Huang Y, Zhang J and Fang Y: MiRNA-339-5p suppresses the malignant development of gastric cancer via targeting ALKBH1. Exp Mol Pathol. 115:1044492020. View Article : Google Scholar : PubMed/NCBI
17	Hong YG, Huang ZP, Liu QZ, E JF, Gao XH, Xin C, Zhang W, Li P and Hao LQ: MicroRNA-95-3p inhibits cell proliferation and metastasis in colorectal carcinoma by HDGF. Biomed J. 43:163–173. 2020. View Article : Google Scholar : PubMed/NCBI
18	Chen Y, Zhou J, Wu X, Huang J, Chen W, Liu D, Zhang J, Huang Y and Xue W: MiR-30a-3p inhibits renal cancer cell invasion and metastasis through targeting ATG12. Transl Androl Urol. 9:646–653. 2020. View Article : Google Scholar : PubMed/NCBI
19	Shang A, Zhou C, Bian G, Chen W, Lu W, Wang W and Li D: miR-381-3p restrains cervical cancer progression by downregulating FGF7. J Cell Biochem. 120:778–789. 2019. View Article : Google Scholar : PubMed/NCBI
20	Xie Y, Qi J, Zhu C, Zhao D and Liao G: MiR-381 functions as a tumor suppressor in gastric cancer by targeting ROCK2. Int J Clin Exp Pathol. 12:164–172. 2019.PubMed/NCBI
21	Hu J, Wu X, Yang C, Rashid K, Ma C, Hu M, Ding Q and Jiang H: Anticancer effect of icaritin on prostate cancer via regulating miR-381-3p and its target gene UBE2C. Cancer Med. 8:7833–7845. 2019. View Article : Google Scholar : PubMed/NCBI
22	He X, Wei Y, Wang Y, Liu L, Wang W and Li N: MiR-381 functions as a tumor suppressor in colorectal cancer by targeting Twist1. Onco Targets Ther. 9:1231–1239. 2016.PubMed/NCBI
23	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
24	Bao W, Cao F, Ni S, Yang J, Li H, Su Z and Zhao B: lncRNA FLVCR1-AS1 regulates cell proliferation, migration and invasion by sponging miR-485-5p in human cholangiocarcinoma. Oncol Lett. 18:2240–2247. 2019.PubMed/NCBI
25	Liu Y, Guo G, Zhong Z, Sun L, Liao L, Wang X, Cao Q and Chen H: Long non-coding RNA FLVCR1-AS1 sponges miR-155 to promote the tumorigenesis of gastric cancer by targeting c-Myc. Am J Transl Res. 11:793–805. 2019.PubMed/NCBI
26	Gao X, Zhao S, Yang X, Zang S and Yuan X: Long non-coding RNA FLVCR1-AS1 contributes to the proliferation and invasion of lung cancer by sponging miR-573 to upregulate the expression of E2F transcription factor 3. Biochem Biophys Res Commun. 505:931–938. 2018. View Article : Google Scholar : PubMed/NCBI
27	Zhang L, Cheng H, Yue Y, Li S, Zhang D and He R: TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovasc Pathol. 33:6–15. 2018. View Article : Google Scholar : PubMed/NCBI
28	Riaz F and Li D: Non-coding RNA associated competitive endogenous RNA regulatory network: Novel therapeutic approach in liver fibrosis. Curr Gene Ther. 19:305–317. 2019. View Article : Google Scholar : PubMed/NCBI
29	Wu D, Qin BY, Qi XG, Hong LL, Zhong HB and Huang JY: LncRNA AWPPH accelerates the progression of non-small cell lung cancer by sponging miRNA-204 to upregulate CDK6. Eur Rev Med Pharmacol Sci. 24:4281–4287. 2020.PubMed/NCBI
30	Wang X, Chen K and Zhao Z: LncRNA OR3A4 regulated the growth of osteosarcoma cells by modulating the miR-1207-5p/G6PD Signaling. Onco Targets Ther. 13:3117–3128. 2020. View Article : Google Scholar : PubMed/NCBI
31	Meng Q, Wang L, Lv Y, Wu J and Shi W: Deletion of HNF1A-AS1 suppresses the malignant phenotypes of breast cancer cells in vitro and in vivo through targeting miRNA-20a-5p/TRIM32 axis. Cancer Biother Radiopharm. Apr 22–2020.(Epub ahead of print). doi: 10.1089/cbr.2019.3168. View Article : Google Scholar
32	Zhang J, Wei Y, Min J, Wang Y, Yin L, Cao G and Shen H: Knockdown of RAP2A gene expression suppresses cisplatin resistance in gastric cancer cells. Oncol Lett. 19:350–358. 2020.
33	Zheng X, Zhao W, Ji P, Zhang K, Jin J, Feng M, Wang F, Zheng S and Wang X: High expression of Rap2A is associated with poor prognosis of patients with hepatocellular carcinoma. Int J Clin Exp Pathol. 10:9607–9613. 2017.PubMed/NCBI
34	Wu JX, Du WQ, Wang XC, Wei LL, Huo FC, Pan YJ, Wu XJ and Pei DS: Rap2a serves as a potential prognostic indicator of renal cell carcinoma and promotes its migration and invasion through up-regulating p-Akt. Sci Rep. 7:66232017. View Article : Google Scholar : PubMed/NCBI
35	Wu JX, Zhang DG, Zheng JN and Pei DS: Rap2a is a novel target gene of p53 and regulates cancer cell migration and invasion. Cell Signal. 27:1198–1207. 2015. View Article : Google Scholar : PubMed/NCBI