A critical role of mir-199a in the cell biological behaviors of colorectal cancer

Diagnostic Pathology

Xuebao Zheng¹  Ying Deng¹  Cancan Guo¹  Yuzhen Zhu¹  Qiong Wu¹  Liping Pang¹  Hua Ye¹ 

[1] Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang 524023, Guangdong, China

关键词: Vascular endothelial growth factor;    Hypoxia-inducible factor 1α;    In vitro;    Cell lines;    Colorectal cancer;    MiR-199a;   

Others  :  1217731
DOI  :  10.1186/s13000-015-0260-x

 received in 2014-11-25, accepted in 2015-04-06,  发布年份 2015

【 摘 要 】

Background

Colorectal cancer (CRC) is one of the most common cancer and the leading causes of cancer mortality worldwide. The critical role of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are important in the cancer development.

Methods

The purpose of this study was to investigate the association of miR-199a expression in CRC and non-tumor tissues as well as assessed the effect of miR-199a on biological behaviors including cell proliferation, apoptosis, migration and invasion of CRC cells. The expression of miR-199a was distinctly decreased in colorectal cancer tissues compared with non-neoplastic colorectal tissues.

Results

In this study, we found that miR-199a down-regulation was associated with the CRC and metastasis incidence. Advanced study showed that miR-199a up-regulation would lead to decreased CRC proliferation, migration and invasion. However, no significant association of miR-199a treatment and apoptosis rate and cell-cycle were detected in this study. The detection for the mechanisms of miR-199a on the development of CRC showed that the anticarcinogenic effect of miR-199a might be produced through HIF-1α/VEGF pathway.

Conclusion

It was found that miR-199a would reduce the proliferation, migration and invasion. However, overexpression of miR-199a on the apoptosis rate and cell cycles showed no significant results. The potential functionary mechanism of miR-199a might through HIF-1α/VEGF pathway.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9806714131513041.

【 授权许可】

   
2015 Ye et al.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Stegeman I, Van Doorn SC, Mundt MW, Mallant-Hent RC, Bongers E, Elferink MA et al.. Participation, yield, and interval carcinomas in three rounds of biennial FIT-based colorectal cancer screening. Cancer Epidemiol. 2015; 39:388-393.
• [2]Wu XY, Fu ZX, Wang XH, Shen W. Identification of differential proteins in colon cancer SW480 cells with HIF1-alpha silence by proteome analysis. Neoplasma. 2010; 57:299-305.
• [3]Kim JH, Park MY, Kim CN, Kim KH, Kang HB, Kim KD et al.. Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1alpha in human colon carcinoma: impact of ESM-1 on prognosis and its correlation with clinicopathological features. Oncol Rep. 2012; 28:1701-1708.
• [4]Yoshimura H, Dhar DK, Kohno H, Kubota H, Fujii T, Ueda S et al.. Prognostic impact of hypoxia-inducible factors 1alpha and 2alpha in colorectal cancer patients: correlation with tumor angiogenesis and cyclooxygenase-2 expression. Clin Cancer Res. 2004; 10:8554-8560.
• [5]Atsumi T, Singh R, Sabharwal L, Bando H, Meng J, Arima Y et al.. Inflammation amplifier, a new paradigm in cancer biology. Cancer Res. 2014; 74:8-14.
• [6]Suzuki S, Dobashi Y, Hatakeyama Y, Tajiri R, Fujimura T, Heldin CH et al.. Clinicopathological significance of platelet-derived growth factor (PDGF)-B and vascular endothelial growth factor-A expression, PDGF receptor-beta phosphorylation, and microvessel density in gastric cancer. BMC Cancer. 2010; 10:659. BioMed Central Full Text
• [7]Ueda J, Ho JC, Lee KL, Kitajima S, Yang H, Sun W et al.. The Hypoxia-Inducible Epigenetic Regulators Jmjd1a and G9a Provide a Mechanistic Link between Angiogenesis and Tumor Growth. Mol Cell Biol. 2014; 34:3702-3720.
• [8]Mattis AN, Song G, Hitchner K, Kim RY, Lee AY, Sharma AD et al.. A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver. Hepatology. 2014; 61:141-52.
• [9]Harapan H, Fitra F, Ichsan I, Mulyadi M, Miotto P, Hasan NA et al.. The roles of microRNAs on tuberculosis infection: meaning or myth? Tuberculosis (Edinb). 2013; 93:596-605.
• [10]Berstad P, Loberg M, Larsen IK, Kalager M, Holme O, Botteri E, Bretthauer M, Hoff G. Long-term lifestyle changes after colorectal cancer screening: randomised controlled trial. Gut 2014.Sep 2. Epub
• [11]Kong Y, Bai PS, Sun H, Nan KJ, Chen NZ, Qi XG. The deoxycholic acid targets miRNA-dependent CAC1 gene expression in multidrug resistance of human colorectal cancer. Int J Biochem Cell Biol. 2012; 44:2321-2332.
• [12]Ding G, Huang G, Liu HD, Liang HX, Ni YF, Ding ZH et al.. MiR-199a suppresses the hypoxia-induced proliferation of non-small cell lung cancer cells through targeting HIF1alpha. Mol Cell Biochem. 2013; 384:173-180.
• [13]Wang J, Huang SK, Zhao M, Yang M, Zhong JL, Gu YY et al.. Identification of a circulating microRNA signature for colorectal cancer detection. PLoS One. 2014; 9: Article ID e87451
• [14]Qu Y, Huang X, Li Z, Liu J, Wu J, Chen D et al.. miR-199a-3p inhibits aurora kinase A and attenuates prostate cancer growth: new avenue for prostate cancer treatment. Am J Pathol. 2014; 184:1541-1549.
• [15]Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A et al.. microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer. 2013; 132:2479-2491.
• [16]Wang W, Zhao LJ, Tan YX, Ren H, Qi ZT. Identification of deregulated miRNAs and their targets in hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol. 2012; 18:5442-5453.
• [17]Cardin R, Piciocchi M, Sinigaglia A, Lavezzo E, Bortolami M, Kotsafti A et al.. Oxidative DNA damage correlates with cell immortalization and mir-92 expression in hepatocellular carcinoma. BMC Cancer. 2012; 12:177. BioMed Central Full Text
• [18]Cheng W, Liu T, Wan X, Gao Y, Wang H. MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 2012; 279:2047-2059.
• [19]Tsukigi M, Bilim V, Yuuki K, Ugolkov A, Naito S, Nagaoka A et al.. Re-expression of miR-199a suppresses renal cancer cell proliferation and survival by targeting GSK-3beta. Cancer Lett. 2012; 315:189-197.
• [20]Hu Y, Liu J, Jiang B, Chen J, Fu Z, Bai F et al.. MiR-199a-5p Loss Up-Regulated DDR1 Aggravated Colorectal Cancer by Activating Epithelial-to-Mesenchymal Transition Related Signaling. Dig Dis Sci. 2014; 59:2163-2172.
• [21]Nagaraju GP, Park W, Wen J, Mahaseth H, Landry J, Farris AB et al.. Antiangiogenic effects of ganetespib in colorectal cancer mediated through inhibition of HIF-1alpha and STAT-3. Angiogenesis. 2013; 16:903-917.
• [22]Price TJ, Hardingham JE, Lee CK, Townsend AR, Wrin JW, Wilson K et al.. Prognostic impact and the relevance of PTEN copy number alterations in patients with advanced colorectal cancer (CRC) receiving bevacizumab. Cancer Med. 2013; 2:277-285.
• [23]Shimomura M, Hinoi T, Kuroda S, Adachi T, Kawaguchi Y, Sasada T et al.. Overexpression of hypoxia inducible factor-1 alpha is an independent risk factor for recurrence after curative resection of colorectal liver metastases. Ann Surg Oncol. 2013; 20 Suppl 3:S527-536.
• [24]Joshi HP, Subramanian IV, Schnettler EK, Ghosh G, Rupaimoole R, Evans C et al.. Dynamin 2 along with microRNA-199a reciprocally regulate hypoxia-inducible factors and ovarian cancer metastasis. Proc Natl Acad Sci U S A. 2014; 111:5331-5336.
• [25]He J, Jing Y, Li W, Qian X, Xu Q, Li FS et al.. Roles and mechanism of miR-199a and miR-125b in tumor angiogenesis. PLoS One. 2013; 8: Article ID e56647
• [26]Jia XQ, Cheng HQ, Qian X, Bian CX, Shi ZM, Zhang JP et al.. Lentivirus-mediated overexpression of microRNA-199a inhibits cell proliferation of human hepatocellular carcinoma. Cell Biochem Biophys. 2012; 62:237-244.