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Article

MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation

  • Authors:
    • Zhe Zhang
    • Xiaohua Zhong
    • Yipin Xiao
    • Chao Chen
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, Huizhou Municipal Central Hospital, Huizhou, Guangdong 516001, P.R. China
  • Pages: 619-629
    |
    Published online on: October 18, 2018
       https://doi.org/10.3892/or.2018.6806
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Abstract

Colorectal cancer (CRC) is the most commonly diagnosed tumor worldwide. However, the molecular mechanisms and biological processes of CRC remain unknown. The present study used reverse transcription-quantitative polymerase chain reaction to determine the expression levels of microRNA (miR)-296 in CRC cell lines and tissues. In addition, a miR-296 mimic was transfected into CRC cells, and the effects of miR-296 on cell proliferation and apoptosis were explored by MTT assay and flow cytometry. Luciferase assays were also performed to validate arrestin β1 (ARRB1) as a miR-296 target in SW480 and HCT-116 cells. The results demonstrated that miR-296 is a critical tumor suppressor which was downregulated in CRC patients. Increased expression levels of miR-296 were positively associated with a longer survival time of CRC patients. In addition, it was demonstrated that ARRB1 is a direct downstream target of miR-296. Upregulation of miR-296 in SW480 and HCT-116 cells resulted in suppressed cell growth and increased cell apoptosis through an ARRB1-dependent mechanism. Furthermore, the molecular mechanisms underlying the antitumor effect of miR‑296 in CRC are at least in part due to the inactivation of the RAC-α serine/threonine-protein kinase (AKT) signaling pathway induced by the suppression of ARRB1 expression. Overall, the present study, to the best of the author's knowledge, is the first to demonstrate that the miR-296-ARRB1-AKT signaling pathway forms a critical feedback loop and mediates CRC carcinogenesis, and these findings may introduce a potential therapeutic strategy for the treatment of CRC.
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1 

Wang J, Song YX, Ma B, Wang JJ, Sun JX, Chen XW, Zhao JH, Yang YC and Wang ZN: Regulatory roles of non-coding RNAs in colorectal cancer. Int J Mol Sci. 16:19886–19919. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Konda B, Shum H and Rajdev L: Anti-angiogenic agents in metastatic colorectal cancer. World J Gastrointest Oncol. 7:71–86. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Kocarnik JM, Shiovitz S and Phipps AI: Molecular phenotypes of colorectal cancer and potential clinical applications. Gastroenterol Rep (Oxf). 3:269–276. 2015.PubMed/NCBI

4 

Farazi TA, Hoell JI, Morozov P and Tuschl T: MicroRNAs in human cancer. Adv Exp Med Biol. 774:1–20. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Wang L, Bo X, Zheng Q, Xiao X, Wu L and Li B: miR-296 inhibits proliferation and induces apoptosis by targeting FGFR1 in human hepatocellular carcinoma. FEBS Lett. 590:4252–4262. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Dinami R, Buemi V, Sestito R, Zappone A, Ciani Y, Mano M, Petti E, Sacconi A, Blandino G, Giacca M, et al: Epigenetic silencing of miR-296 and miR-512 ensures hTERT dependent apoptosis protection and telomere maintenance in basal-type breast cancer cells. Oncotarget. 8:95674–95691. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Lee KH, Lin FC, Hsu TI, Lin JT, Guo JH, Tsai CH, Lee YC, Lee YC, Chen CL, Hsiao M, et al: MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1. Biochim Biophys Acta. 1843:2055–2066. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Yan W, Chen J, Chen Z and Chen H: Deregulated miR-296/S100A4 axis promotes tumor invasion by inducing epithelial-mesenchymal transition in human ovarian cancer. Am J Cancer Res. 6:260–269. 2016.PubMed/NCBI

9 

Luo W, Lin Y, Meng S, Guo Y, Zhang J and Zhang W: miRNA-296-3p modulates chemosensitivity of lung cancer cells by targeting CX3CR1. Am J Transl Res. 8:1848–1856. 2016.PubMed/NCBI

10 

Savi F, Forno I, Faversani A, Luciani A, Caldiera S, Gatti S, Foa P, Ricca D, Bulfamante G, Vaira V, et al: miR-296/Scribble axis is deregulated in human breast cancer and miR-296 restoration reduces tumour growth in vivo. Clin Sci (Lond). 127:233–242. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Kunte DP, DelaCruz M, Wali RK, Menon A, Du H, Stypula Y, Patel A, Backman V and Roy HK: Dysregulation of microRNAs in colonic field carcinogenesis: Implications for screening. PLoS One. 7:e455912012. View Article : Google Scholar : PubMed/NCBI

12 

Witherow DS, Garrison TR, Miller WE and Lefkowitz RJ: beta-Arrestin inhibits NF-kappaB activity by means of its interaction with the NF-kappaB inhibitor IkappaBalpha. Proc Natl Acad Sci USA. 101:8603–8607. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Miele E, Po A, Begalli F, Antonucci L, Mastronuzzi A, Marras CE, Carai A, Cucchi D, Abballe L, Besharat ZM, et al: β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells. BMC Cancer. 17:4882017. View Article : Google Scholar : PubMed/NCBI

14 

Kraemer A, Barjaktarovic Z, Sarioglu H, Winkler K, Eckardt-Schupp F, Tapio S, Atkinson MJ and Moertl S: Cell survival following radiation exposure requires miR-525-3p mediated suppression of ARRB1 and TXN1. PLoS One. 8:e774842013. View Article : Google Scholar : PubMed/NCBI

15 

Kang J, Shi Y, Xiang B, Qu B, Su W, Zhu M, Zhang M, Bao G, Wang F, Zhang X, et al: A nuclear function of beta-arrestin1 in GPCR signaling: Regulation of histone acetylation and gene transcription. Cell. 123:833–847. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Parathath SR, Mainwaring LA, Fernandez-L A, Guldal CG, Nahlé Z and Kenney AM: β-Arrestin-1 links mitogenic sonic hedgehog signaling to the cell cycle exit machinery in neural precursors. Cell Cycle. 9:4013–4024. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Yang Y, Guo Y, Tan S, Ke B, Tao J, Liu H, Jiang J, Chen J, Chen G and Wu B: β-Arrestin1 enhances hepatocellular carcinogenesis through inflammation-mediated Akt signalling. Nat Commun. 6:73692015. View Article : Google Scholar : PubMed/NCBI

18 

Zecchini V, Madhu B, Russell R, Pértega-Gomes N, Warren A, Gaude E, Borlido J, Stark R, Ireland-Zecchini H, Rao R, et al: Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer. EMBO J. 33:1365–1382. 2014.PubMed/NCBI

19 

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

20 

Ma H, Wang L, Zhang T, Shen H and Du J: Loss of β-arrestin1 expression predicts unfavorable prognosis for non-small cell lung cancer patients. Tumour Biol. 37:1341–1347. 2016. View Article : Google Scholar : PubMed/NCBI

21 

Hong L, Han Y, Zhang H, Li M, Gong T, Sun L, Wu K, Zhao Q and Fan D: The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann Surg. 251:1056–1063. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Wang Q, Qian J, Wang J, Luo C, Chen J, Hu G and Lu Y: Knockdown of RLIP76 expression by RNA interference inhibits invasion, induces cell cycle arrest, and increases chemosensitivity to the anticancer drug temozolomide in glioma cells. J Neurooncol. 112:73–82. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Shivapurkar N, Mikhail S, Navarro R, Bai W, Marshall J, Hwang J, Pishvaian M, Wellstein A and He AR: Decrease in blood miR-296 predicts chemotherapy resistance and poor clinical outcome in patients receiving systemic chemotherapy for metastatic colon cancer. Int J Colorectal Dis. 28:8872013. View Article : Google Scholar : PubMed/NCBI

24 

He Z, Yu L, Luo S, Li M, Li J, Li Q, Sun Y and Wang C: miR-296 inhibits the metastasis and epithelial-mesenchymal transition of colorectal cancer by targeting S100A4. BMC Cancer. 17:1402017. View Article : Google Scholar : PubMed/NCBI

25 

Fu Q, Song X, Liu Z, Deng X, Luo R, Ge C, Li R, Li Z, Zhao M, Chen Y, et al: miRomics and proteomics reveal a miR-296-3p/PRKCA/FAK/Ras/c-Myc feedback loop modulated by HDGF/DDX5/β-catenin complex in lung adenocarcinoma. Clin Cancer Res. 23:6336–6350. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Deng X, Liu Z, Liu X, Fu Q, Deng T, Lu J, Liu Y, Liang Z, Jiang Q, Cheng C, et al: miR-296-3p negatively regulated by nicotine stimulates cytoplasmic translocation of c-Myc via MK2 to suppress chemotherapy resistance. Mol Ther. 26:1066–1081. 2018. View Article : Google Scholar : PubMed/NCBI

27 

Li H, Li J, Shi B and Chen F: MicroRNA-296 targets AKT2 in pancreatic cancer and functions as a potential tumor suppressor. Mol Med Rep. 16:466–472. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Ma L and Pei G: Beta-arrestin signaling and regulation of transcription. J Cell Sci. 120:213–218. 2007. View Article : Google Scholar : PubMed/NCBI

29 

Zhang YX, Li XF, Yuan GQ, Hu H, Song XY, Li JY, Miao XK, Zhou TX, Yang WL, Zhang XW, et al: β-Arrestin 1 has an essential role in neurokinin-1 receptor-mediated glioblastoma cell proliferation and G2/M phase transition. J Biol Chem. 292:8933–8947. 2017. View Article : Google Scholar : PubMed/NCBI

30 

Guzińska-Ustymowicz K, Pryczynicz A, Kemona A and Czyzewska J: Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res. 29:3049–3052. 2009.PubMed/NCBI

31 

Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ and Levin B: bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 55:237–241. 1995.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Zhong X, Xiao Y and Chen C: MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncol Rep 41: 619-629, 2019.
APA
Zhang, Z., Zhong, X., Xiao, Y., & Chen, C. (2019). MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncology Reports, 41, 619-629. https://doi.org/10.3892/or.2018.6806
MLA
Zhang, Z., Zhong, X., Xiao, Y., Chen, C."MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation". Oncology Reports 41.1 (2019): 619-629.
Chicago
Zhang, Z., Zhong, X., Xiao, Y., Chen, C."MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation". Oncology Reports 41, no. 1 (2019): 619-629. https://doi.org/10.3892/or.2018.6806
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Z, Zhong X, Xiao Y and Chen C: MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncol Rep 41: 619-629, 2019.
APA
Zhang, Z., Zhong, X., Xiao, Y., & Chen, C. (2019). MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation. Oncology Reports, 41, 619-629. https://doi.org/10.3892/or.2018.6806
MLA
Zhang, Z., Zhong, X., Xiao, Y., Chen, C."MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation". Oncology Reports 41.1 (2019): 619-629.
Chicago
Zhang, Z., Zhong, X., Xiao, Y., Chen, C."MicroRNA-296 inhibits colorectal cancer cell growth and enhances apoptosis by targeting ARRB1-mediated AKT activation". Oncology Reports 41, no. 1 (2019): 619-629. https://doi.org/10.3892/or.2018.6806
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