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Article

Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression

  • Authors:
    • Meiya Chen
    • Mengjie Lin
    • Xiaozhong Wang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Pathology, Xiamen University, Zhongshan Hospital, Xiamen, Fujian 361004, P.R. China
  • Pages: 619-626
    |
    Published online on: November 24, 2017
       https://doi.org/10.3892/or.2017.6110
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Abstract

The microRNA miR-19a is closely related to tumor formation and development and is a key oncogene. Previous studies have demonstrated that miR-19a is upregulated in multiple cancer types, including colorectal cancer (CRC). However, most of these experiments were performed in vitro, and consequently, the mechanisms underlying the effects of miR-19a on CRC are still unclear. Therefore, in the present study, we investigated the role of miR-19a in the development of solid CRC tumors. We generated KRAS 3'UTR-Mut by deleting the predicted binding site for miR-19a in KRAS, and observed that the expression of a reporter gene containing the KRAS 3'UTR in HCT116 cells was suppressed by miR-19a, while that of a reporter gene with mutant KRAS 3'UTR was unaffected by miR-19a. We observed that high miR-19a levels reduced KRAS expression. In the tube formation assay, overexpression of miR-19a exhibited anti-angiogenesis effects, which were rescued by KRAS expression. We established a nude mouse xenograft model to investigate the specific role of miR-19a in solid tumors. The results revealed that the sizes of xenograft tumors and density of blood vessels developed from HCT116 cells expressing miR-19a were smaller/lower compared with those of the control. KRAS and VEGFA levels were also reduced. In conclusion, our results revealed that miR-19a overexpression supressed KRAS expression and angiogenesis in CRC, indicating possibilities of using miR-19a in future therapeutic applications.
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1 

Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Boutin AT, Liao WT, Wang M, Hwang SS, Karpinets TV, Cheung H, Chu GC, Jiang S, Hu J, Chang K, et al: Oncogenic Kras drives invasion and maintains metastases in colorectal cancer. Genes Dev. 31:370–382. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Taieb J, Le Malicot K, Shi Q, Penault Lorca F, Bouché O, Tabernero J, Mini E, Goldberg RM, Folprecht G, Luc Van Laethem J, et al: Prognostic value of BRAF and KRAS mutations in MSI and MSS stage III colon cancer. J Natl Cancer Inst. 109:pii: djw2722016. View Article : Google Scholar

4 

Yi R, Li Y, Wang FL, Miao G, Qi RM and Zhao YY: MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer. World J Gastrointest Oncol. 8:330–340. 2016. View Article : Google Scholar : PubMed/NCBI

5 

He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, et al: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Lanza G, Ferracin M, Gafà R, Veronese A, Spizzo R, Pichiorri F, Liu CG, Calin GA, Croce CM and Negrini M: mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol Cancer. 6:542007. View Article : Google Scholar : PubMed/NCBI

7 

Diosdado B, van de Wiel MA, Terhaar Sive Droste JS, Mongera S, Postma C, Meijerink WJ, Carvalho B and Meijer GA: MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer. 101:707–714. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Ma H, Pan JS, Jin LX, Wu J, Ren YD, Chen P, Xiao C and Han J: MicroRNA-17~92 inhibits colorectal cancer progression by targeting angiogenesis. Cancer Lett. 376:293–302. 2016. View Article : Google Scholar : PubMed/NCBI

9 

Olive V, Bennett MJ, Walker JC, Ma C, Jiang I, Cordon-Cardo C, Li QJ, Lowe SW, Hannon GJ and He L: miR-19 is a key oncogenic component of mir-17-92. Genes Dev. 23:2839–2849. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Yamamoto K, Ito S, Hanafusa H, Shimizu K and Ouchida M: Uncovering direct targets of miR-19a involved in lung cancer progression. PLoS One. 10:e01378872015. View Article : Google Scholar : PubMed/NCBI

11 

Lu WD, Zuo Y, Xu Z and Zhang M: MiR-19a promotes epithelial-mesenchymal transition through PI3K/AKT pathway in gastric cancer. World J Gastroenterol. 21:4564–4573. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Zhang J, Xiao Z, Lai D, Sun J, He C, Chu Z, Ye H, Chen S and Wang J: miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. Br J Cancer. 107:352–359. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Landskroner-Eiger S, Qiu C, Perrotta P, Siragusa M, Lee MY, Ulrich V, Luciano AK, Zhuang ZW, Corti F, Simons M, et al: Endothelial miR-17~92 cluster negatively regulates arteriogenesis via miRNA-19 repression of WNT signaling. Proc Natl Acad Sci USA. 112:pp. 12812–12817. 2015; View Article : Google Scholar : PubMed/NCBI

14 

Cellura D, Pickard K, Quaratino S, Parker H, Strefford JC, Thomas GJ, Mitter R, Mirnezami AH and Peake NJ: miR-19-mediated inhibition of transglutaminase-2 leads to enhanced invasion and metastasis in colorectal cancer. Mol Cancer Res. 13:1095–1105. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Yu G, Li H, Wang X, Wu T, Zhu J, Huang S, Wan Y and Tang J: MicroRNA-19a targets tissue factor to inhibit colon cancer cells migration and invasion. Mol Cell Biochem. 380:239–247. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Xiao C, Calado DP, Galler G, Thai TH, Patterson HC, Wang J, Rajewsky N, Bender TP and Rajewsky K: MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell. 165:10272016. 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-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Guo H, Jia Y, Shang M, Zhang Y, Xie F, Wang H, Yuan M, Yuan L and Ye J: Comparison of two in vitro angiogenesis assays for evaluating the effects of netrin-1 on tube formation. Acta Biochim Biophys Sin. 46:810–816. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Ponce ML: Tube formation: An in vitro matrigel angiogenesis assay. Methods Mol Biol. 467:183–188. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Simons M and Eichmann A: Molecular controls of arterial morphogenesis. Circ Res. 116:1712–1724. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Yeh YW, Cheng CC, Yang ST, Tseng CF, Chang TY, Tsai SY, Fu E, Chiang CP, Liao LC, Tsai PW, et al: Targeting the VEGF-C/VEGFR3 axis suppresses Slug-mediated cancer metastasis and stemness via inhibition of KRAS/YAP1 signaling. Oncotarget. 8:5603–5618. 2017.PubMed/NCBI

22 

Chakraborty C, Sharma AR, Patra BC, Bhattacharya M, Sharma G and Lee SS: MicroRNAs mediated regulation of MAPK signaling pathways in chronic myeloid leukemia. Oncotarget. 7:42683–42697. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Y, Urbich C, Hofmann WK, Zeiher AM and Dimmeler S: Members of the microRNA-17-92 cluster exhibit a cell-intrinsic antiangiogenic function in endothelial cells. Blood. 115:4944–4950. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Mihalache A and Rogoveanu I: Angiogenesis factors involved in the pathogenesis of colorectal cancer. Curr Health Sci J. 40:5–11. 2014.PubMed/NCBI

25 

Shinkaruk S, Bayle M, Laïn G and Déléris G: Vascular endothelial cell growth factor (VEGF), an emerging target for cancer chemotherapy. Curr Med Chem Anticancer Agents. 3:95–117. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Ikeda N, Nakajima Y, Sho M, Adachi M, Huang CL, Iki K, Kanehiro H, Hisanaga M, Nakano H and Miyake M: The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic carcinoma. Cancer. 92:488–499. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Qiu Y, Yu H, Shi X, Xu K, Tang Q, Liang B, Hu S, Bao Y, Xu J, Cai J, et al: microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A. Cell Prolif. 49:69–78. 2016. View Article : Google Scholar : PubMed/NCBI

28 

Matsuo Y, Campbell PM, Brekken RA, Sung B, Ouellette MM, Fleming JB, Aggarwal BB, Der CJ and Guha S: K-Ras promotes angiogenesis mediated by immortalized human pancreatic epithelial cells through mitogen-activated protein kinase signaling pathways. Mol Cancer Res. 7:799–808. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Ren J, Li G, Ge J, Li X and Zhao Y: Is K-ras gene mutation a prognostic factor for colorectal cancer: A systematic review and meta-analysis. Dis Colon Rectum. 55:913–923. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Tsuchida N, Murugan AK and Grieco M: Kirsten Ras* oncogene: Significance of its discovery in human cancer research. Oncotarget. 7:46717–46733. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Deng Y, Wang L, Tan S, Kim GP, Dou R, Chen D, Cai Y, Fu X, Wang L, Zhu J, et al: KRAS as a predictor of poor prognosis and benefit from postoperative FOLFOX chemotherapy in patients with stage II and III colorectal cancer. Mol Oncol. 9:1341–1347. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Gil Ferreira C, Aran V, Zalcberg-Renault I, Victorino AP, Salem JH, Bonamino MH, Vieira FM and Zalis M: KRAS mutations: Variable incidences in a Brazilian cohort of 8,234 metastatic colorectal cancer patients. BMC Gastroenterol. 14:732014. View Article : Google Scholar : PubMed/NCBI

33 

Friedman RC, Farh KK, Burge CB and Bartel DP: Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19:92–105. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen M, Lin M and Wang X: Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression. Oncol Rep 39: 619-626, 2018.
APA
Chen, M., Lin, M., & Wang, X. (2018). Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression. Oncology Reports, 39, 619-626. https://doi.org/10.3892/or.2017.6110
MLA
Chen, M., Lin, M., Wang, X."Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression". Oncology Reports 39.2 (2018): 619-626.
Chicago
Chen, M., Lin, M., Wang, X."Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression". Oncology Reports 39, no. 2 (2018): 619-626. https://doi.org/10.3892/or.2017.6110
Copy and paste a formatted citation
x
Spandidos Publications style
Chen M, Lin M and Wang X: Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression. Oncol Rep 39: 619-626, 2018.
APA
Chen, M., Lin, M., & Wang, X. (2018). Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression. Oncology Reports, 39, 619-626. https://doi.org/10.3892/or.2017.6110
MLA
Chen, M., Lin, M., Wang, X."Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression". Oncology Reports 39.2 (2018): 619-626.
Chicago
Chen, M., Lin, M., Wang, X."Overexpression of miR-19a inhibits colorectal cancer angiogenesis by suppressing KRAS expression". Oncology Reports 39, no. 2 (2018): 619-626. https://doi.org/10.3892/or.2017.6110
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