MicroRNA‑101 suppresses colorectal cancer progression by negative regulation of Rap1b

Zhou,Zhiyuan; Xu,Hang; Duan,Yantao; Liu,Bin

doi:10.3892/ol.2020.11791

MicroRNA‑101 suppresses colorectal cancer progression by negative regulation of Rap1b

Authors:
- Zhiyuan Zhou
- Hang Xu
- Yantao Duan
- Bin Liu
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Affiliations: Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
Published online on: July 1, 2020 https://doi.org/10.3892/ol.2020.11791
Pages: 2225-2231
Copyright: © Zhou 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 the fourth most lethal malignancy and is the second most common cause of cancer‑associated mortality worldwide. The development of high‑throughput sequencing has enabled the identification of potential biomarkers for the diagnosis and treatment of various types of cancer. Although microRNA‑101 (miR‑101) has been demonstrated to be a potential biomarker of CRC, its detailed mechanisms remain to be fully discovered. In the present study, overall survival analysis was applied to determine the association between miR‑101 and CRC prognosis. Reverse transcription‑quantitative PCR (RT‑qPCR) was used to examine gene expression levels in tissues and cells. Cell proliferative and apoptotic activities were determined by MTT and flow cytometry assays, respectively. Wound healing and Transwell assays were used to examine CRC cell migration and invasion, respectively. In the present study, RT‑qPCR analysis indicated that miR‑101 was significantly downregulated in CRC tissues and cells. However, clinical data collected from The Cancer Genome Atlas revealed no significant association between the expression levels of miR‑101 and the prognosis of CRC. Additionally, miR‑101 inhibited the progression of CRC by directly binding to the 3'‑untranslated region of Ras‑related protein Rap1b (Rap1b). This was associated with downregulation of Rap1b expression. Furthermore, the overexpression of Rap1b promoted miR‑101 mimic‑attenuated CRC cell progression. The present study demonstrated that miR‑101 may be involved in the repression of the CRC progression by forming a negative feedback loop with Rap1b. The findings revealed the interaction between miR‑101 and Rap1b during the progression of CRC, which could aid the development of therapeutic strategies.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
3	Rupaimoole R and Slack FJ: MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 16:203–222. 2017. View Article : Google Scholar : PubMed/NCBI
4	Liu D, Li Y, Luo G, Xiao X, Tao D, Wu X, Wang M, Huang C, Wang L, Zeng F and Jiang G: LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2. Cancer Lett. 388:281–291. 2017. View Article : Google Scholar : PubMed/NCBI
5	Qian K, Liu G, Tang Z, Hu Y, Fang Y, Chen Z and Xu X: The long non-coding RNA NEAT1 interacted with miR-101 modulates breast cancer growth by targeting EZH2. Arch Biochem Biophys. 615:1–9. 2017. View Article : Google Scholar : PubMed/NCBI
6	Liu Y, Tan J, Ou S, Chen J and Chen L: MicroRNA-101-3p suppresses proliferation and migration in hepatocellular carcinoma by targeting the HGF/c-Met pathway. Invest New Drugs. Mar 30–2019.(Epub ahead of print). doi: 10.1007/s10637-019-00766-8.
7	Chen LG, Xia YJ and Cui Y: Upregulation of miR-101 enhances the cytotoxic effect of anticancer drugs through inhibition of colon cancer cell proliferation. Oncol Rep. 38:100–108. 2017. View Article : Google Scholar : PubMed/NCBI
8	Hattori M and Minato N: Rap1 GTPase: Functions, regulation, and malignancy. J Biochem. 134:479–484. 2003. View Article : Google Scholar : PubMed/NCBI
9	Pei W, Tao L, Zhang LW, Zhang S, Cao J, Jiao Y, Tong J and Nie J: Circular RNA profiles in mouse lung tissue induced by radon. Environ Health Prev Med. 22:362017. View Article : Google Scholar : PubMed/NCBI
10	Yang Y, Li M, Yan Y, Zhang J, Sun K, Qu JK, Wang JS and Duan XY: Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer. Oncol Rep. 34:2385–2394. 2015. View Article : Google Scholar : PubMed/NCBI
11	Lin KT, Yeh YM, Chuang CM, Yang SY, Chang JW, Sun SP, Wang YS, Chao KC and Wang LH: Glucocorticoids mediate induction of microRNA-708 to suppress ovarian cancer metastasis through targeting Rap1B. Nat Commun. 6:59172015. View Article : Google Scholar : PubMed/NCBI
12	Huk DJ, Ashtekar A, Magner A, La Perle K and Kirschner LS: Deletion of Rap1b, but not Rap1a or Epac1, reduces protein kinase A-mediated thyroid cancer. Thyroid. 28:1153–1161. 2018. View Article : Google Scholar : PubMed/NCBI
13	Tang Z, Peng H, Chen J, Liu Y, Yan S, Yu G, Chen Q, Tang H and Liu S: Rap1b enhances the invasion and migration of hepatocellular carcinoma cells by up-regulating Twist 1. Exp Cell Res. 367:56–64. 2018. View Article : Google Scholar : PubMed/NCBI
14	Jia Z, Yang Y, Dengyan Z, Chunyang Z, Donglei L, Kai W and Song Z: RAP1B, a DVL2 binding protein, activates Wnt/beta-catenin signaling in esophageal squamous cell carcinoma. Gene. 611:15–20. 2017. View Article : Google Scholar : PubMed/NCBI
15	Li Z, Xu C, Ding B, Gao M, Wei X and Ji N: Long non-coding RNA MALAT1 promotes proliferation and suppresses apoptosis of glioma cells through derepressing Rap1B by sponging miR-101. J Neurooncol. 134:19–28. 2017. View Article : Google Scholar : PubMed/NCBI
16	Sheng Y, Ding S, Chen K, Chen J, Wang S, Zou C, Zhang J, Cao Y, Huang A and Tang H: Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis. Biochem Cell Biol. 92:152–162. 2014. View Article : Google Scholar : PubMed/NCBI
17	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
18	Joseph JV, Conroy S, Pavlov K, Sontakke P, Tomar T, Eggens-Meijer E, Balasubramaniyan V, Wagemakers M, den Dunnen WF and Kruyt FA: Hypoxia enhances migration and invasion in glioblastoma by promoting a mesenchymal shift mediated by the HIF1α-ZEB1 axis. Cancer Lett. 359:107–116. 2015. View Article : Google Scholar : PubMed/NCBI
19	Collins FS and Barker AD: Mapping the cancer genome. Pinpointing the genes involved in cancer will help chart a new course across the complex landscape of human malignancies. Sci Am. 296:50–57. 2007. View Article : Google Scholar : PubMed/NCBI
20	Li L, Zhu Z, Zhao Y, Zhang Q, Wu X, Miao B, Cao J and Fei S: FN1, SPARC, and SERPINE1 are highly expressed and significantly related to a poor prognosis of gastric adenocarcinoma revealed by microarray and bioinformatics. Sci Rep. 9:78272019. View Article : Google Scholar : PubMed/NCBI
21	Hassanlou M, Soltani BM, Medlej A, Kay M and Mowla SJ: Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells. Biol Chem. Nov 8–2019.(Epub ahead of print). doi: 10.1515/hsz-2018-0421.
22	Zhu QL, Zhan DM, Chong YK, Ding L and Yang YG: MiR-652-3p promotes bladder cancer migration and invasion by targeting KCNN3. Eur Rev Med Pharmacol Sci. 23:8806–8812. 2019.PubMed/NCBI
23	Cao C, Xu Y, Du K, Mi C, Yang C, Xiang L, Xie Y and Liu W: LINC01303 functions as a competing endogenous RNA to regulate EZH2 expression by sponging miR-101-3p in gastric cancer. J Cell Mol Med. 23:7342–7348. 2019. View Article : Google Scholar : PubMed/NCBI
24	Zhang H, Wang X, Hu B, Zhang F, Wei H and Li L: Circular RNA ZFR accelerates non-small cell lung cancer progression by acting as a miR-101-3p sponge to enhance CUL4B expression. Artif Cells Nanomed Biotechnol. 47:3410–3416. 2019. View Article : Google Scholar : PubMed/NCBI
25	Liu C, Sun Y, She X, Tu C, Cheng X, Wang L, Yu Z, Li P, Liu Q, Yang H, et al: CASC2c as an unfavorable prognosis factor interacts with miR-101 to mediate astrocytoma tumorigenesis. Cell Death Dis. 8:e26392017. View Article : Google Scholar : PubMed/NCBI
26	Jiang M, Xu B, Li X, Shang Y, Chu Y, Wang W, Chen D, Wu N, Hu S, Zhang S, et al: O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit. Oncogene. 38:301–316. 2019. View Article : Google Scholar : PubMed/NCBI
27	Xiong WC, Han N, Wu N, Zhao KL, Han C, Wang HX, Ping GF, Zheng PF, Feng H, Qin L and He P: Interplay between long noncoding RNA ZEB1-AS1 and miR-101/ZEB1 axis regulates proliferation and migration of colorectal cancer cells. Am J Transl Res. 10:605–617. 2018.PubMed/NCBI
28	Wilson JM, Lorimer E, Tyburski MD and Williams CL: β-Adrenergic receptors suppress Rap1B prenylation and promote the metastatic phenotype in breast cancer cells. Cancer Biol Ther. 16:1364–1374. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhang M, Zhou S, Zhang L, Zhang J, Cai H, Zhu J, Huang C and Wang J: miR-518b is down-regulated, and involved in cell proliferation and invasion by targeting Rap1b in esophageal squamous cell carcinoma. FEBS Lett. 586:3508–3521. 2012. View Article : Google Scholar : PubMed/NCBI
30	Li Y, Liu Y, Shi F, Cheng L and She J: Knockdown of Rap1b enhances apoptosis and autophagy in gastric cancer cells via the PI3K/Akt/mTOR pathway. Oncol Res. 24:287–293. 2016. View Article : Google Scholar : PubMed/NCBI
31	Peng H, Luo J, Hao H, Hu J, Xie SK, Ren D and Rao B: MicroRNA-100 regulates SW620 colorectal cancer cell proliferation and invasion by targeting RAP1B. Oncol Rep. 31:2055–2062. 2014. View Article : Google Scholar : PubMed/NCBI
32	Guo H, Hu X, Ge S, Qian G and Zhang J: Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation. Int J Biochem Cell Biol. 44:1465–1472. 2012. View Article : Google Scholar : PubMed/NCBI