Expression and Clinical Significance of MicroRNA-376a in Colorectal Cancer

  • Mo, Zhan-Hao (Endoscopy Center, China-Japan Union Hospital, Jilin University) ;
  • Wu, Xiao-Dong (Scientific Research Center, China-Japan Union Hospital, Jilin University) ;
  • Li, Shuo (Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital, Jilin University) ;
  • Fei, Bing-Yuan (Department of General Surgery, China-Japan Union Hospital, Jilin University) ;
  • Zhang, Bin (Endoscopy Center, China-Japan Union Hospital, Jilin University)
  • Published : 2014.11.28


The incidence of colorectal cancer (CRC) is increasing in many Asian countries and microRNAs have already been proven to be associated with tumorigenesis. Currently, microRNA-376a (miR-376a) expression and association with clinical factors in CRC remains unclear. In this study, real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was carried out on 53 matched pairs of CRC and adjacent normal mucosa to investigate the expression levels of miR-376a. According to the high or low expression of miR-376a, patients were divided into two groups. The relationship between miR-376a expression and clinicopathological factors of 53 patients was evaluated. Survival analysis of 53 CRC patients was performed with clinical follow-up information and survival curves were assessed by the Kaplan-Meier method. Immunohistochemistry (IHC) staining was performed on sections of paraffin-embedded tissue to investigate the vascular endothelial growth factor (VEGF) expression. MiR-376a showed low expression in cancer tissues compared to the adjacent normal tissues and altered high miR-376a expression tended to be positively correlated with advanced lymph node metastasis and shorter patient survival. VEGF IHC positivity was significantly more common in patients with high expression levels of miR-376a.Those results demonstrated that miR-376a may be a meaningful prognostic biomarker and potential therapeutic target in colorectal cancer.


Supported by : Jilin Provincial Science and Technology Department


  1. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  2. Brennecke J, Hipfner DR, Stark A, et al (2003). bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell, 113, 25-36.
  3. Bruderer M, Alini M, Stoddart MJ (2013). Role of HOXA9 and VEZF1 in endothelial biology. J Vasc Res, 50, 265-78.
  4. Cuk K, Zucknick M, Madhavan D, et al (2013). Plasma microRNA panel for minimally invasive detection of breast cancer. PLoS One, 8, 76729.
  5. Farazi TA, Spitzer JI, Morozov P, et al (2011). miRNAs in human cancer. J Pathol, 223, 102-15.
  6. Kelley RK, Wang G, Venook AP (2011). Biomarker use in colorectal cancer therapy. J Natl Compr Canc Netw, 9, 1293-302.
  7. Kunte DP, DelaCruz M, Wali RK, et al (2012). Dysregulation of microRNAs in colonic field carcinogenesis: implications for screening. PLoS One, 7, 45591.
  8. Liu K, Li G, Fan C, et al (2012). Increased expression of microRNA-221 in gastric cancer and its clinical significance. J Int Med Res, 40, 467-74.
  9. Liu Y, Zhou Y, Feng X, et al (2014). Low expression of microRNA-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer, 53, 358-65.
  10. Lou X, Qi X, Zhang Y, et al (2013). Decreased expression of microRNA-625 is associated with tumor metastasis and poor prognosis in patients with colorectal cancer. J Surg Oncol, 108, 230-5.
  11. Lu S, Wang S, Geng S, et al (2013). Upregulation of microRNA-224 confers a poor prognosis in glioma patients. Clin Transl Oncol, 15, 569-74.
  12. Luo X, Burwinkel B, Tao S, et al (2011). MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol Biomarkers Prev, 20, 1272-86.
  13. Ng SC, Wong SH (2013). Colorectal cancer screening in Asia. Br Med Bull, 105, 29-42.
  14. Nishimura J, Handa R, Yamamoto H, et al (2012). microRNA-181a is associated with poor prognosis of colorectal cancer. Oncol Rep, 28, 2221-6.
  15. Peng HH, Zhang YD, Gong LS, et al (2013). Increased expression of microRNA-335 predicts a favorable prognosis in primary gallbladder carcinoma. Onco Targets Ther, 6, 1625-30.
  16. Shen SN, Wang LF, Jia YF, et al (2013). Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer. Diagn Pathol, 8, 69.
  17. Sung JJ, Lau JY, Goh KL, et al (2005). Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol, 6, 871-6.
  18. Toyama T, Kondo N, Endo Y, et al (2012). High expression of microRNA-210 is an independent factor indicating a poor prognosis in Japanese triple-negative breast cancer patients. Jpn J Clin Oncol, 42, 256-63.
  19. van den Berg A, Mols J, Han J (2008). RISC-target interaction: cleavage and translational suppression. Biochim Biophys Acta, 1779, 668-77.
  20. Wan SM, Lv F, Guan T (2012). Identification of genes and microRNAs involved in ovarian carcinogenesis. Asian Pac J Cancer Prev, 13, 3997-4000.
  21. Wang S, Li Q, Wang K, et al (2013). Decreased expression of microRNA-31 associates with aggressive tumor progression and poor prognosis in patients with bladder cancer. Clin Transl Oncol, 15, 849-54.
  22. Warren RS, Yuan H, Matli MR, et al (1996). Induction of vascular endothelial growth factor by insulin-like growth factor 1 in colorectal carcinoma. J Biol Chem, 271, 29483-8.
  23. Wu W, Yang J, Feng X, et al (2013a). MicroRNA-32 (miR-32) regulates phosphatase and tensin homologue (PTEN) expression and promotes growth, migration, and invasion in colorectal carcinoma cells. Mol Cancer, 12, 30.
  24. Wu W, Yang P, Feng X, et al (2013b). The relationship between and clinical significance of MicroRNA-32 and phosphatase and tensin homologue expression in colorectal cancer. Genes Chromosomes Cancer, 52, 1133-40.
  25. Xiao ZG, Deng ZS, Zhang YD, et al (2013). Clinical significance of microRNA-93 downregulation in human colon cancer. Eur J Gastroenterol Hepatol, 25, 296-301.
  26. Xu T, Liu X, Han L, et al (2014). Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer. Clin Transl Oncol, 16, 469-75.
  27. Zehavi L, Avraham R, Barzilai A, et al (2012). Silencing of a large microRNA cluster on human chromosome 14q32 in melanoma: biological effects of mir-376a and mir-376c on insulin growth factor 1 receptor. Mol Cancer, 11, 44.
  28. Zhao BS, Liu SG, Wang TY, et al (2013). Screening of microRNA in patients with esophageal cancer at same tumor node metastasis stage with different prognoses. Asian Pac J Cancer Prev, 14, 139-43.
  29. Zheng Y, Yin L, Chen H, et al (2012). miR-376a suppresses proliferation and induces apoptosis in hepatocellular carcinoma. FEBS Lett, 586, 2396-403.

Cited by

  1. Prognostic and Predictive Biomarkers in Colorectal Cancer: Implications for the Clinical Surgeon vol.22, pp.11, 2015,
  2. miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy vol.34, pp.1, 2015,
  3. Gene and miRNA expression signature of Lewis lung carcinoma LLC1 cells in extracellular matrix enriched microenvironment vol.16, pp.1, 2016,
  4. MiR-944 functions as a novel oncogene and regulates the chemoresistance in breast cancer vol.37, pp.2, 2016,
  5. MiR-376a suppresses the proliferation and invasion of non-small-cell lung cancer by targeting c-Myc vol.42, pp.1, 2017,
  6. Biological effects and clinical characteristics of microRNA-106a in human colorectal cancer vol.14, pp.1, 2017,