Abstract
miRNA polymorphisms are recently identified as a risk factor for various cancers, and it is associated with change in the expression of target genes in vitro. rs11614913 polymorphism in miR196a2 was associated with risk of glioma in Chinese population. In this study, we have evaluated the role of rs11614913 polymorphism and glioma risk in Indian population in 180 cases and controls. Seventy-two glioma tissue-blood pairs were also assessed for mutation in this SNP. Further, the effect of this polymorphism on mature miR196a2 expression and HOXC8 gene expression was analysed in 33 glioma tissue samples with different genotypes. Allelic discrimination assay was performed for genotyping and quantitative real time PCR for the expression of miR196a2 and HOXC8 gene. We could not find any association between rs11614913 polymorphism and glioma risk in Indian population. The rs11614913 genotyping of glioma tissue and blood pair revealed presence of mutations showing changes from C to T allele in majority of samples. The expression of the mature miR196a2 was significantly high in glioma samples, but there was no difference in expression with genotype. HOXC8 gene expression was not significantly different in glioma tissue when compared to non-glioma and interestingly there was a significant difference in expression with different genotypes, especially TT genotype was showing over expression when compared to other genotypes. Our study suggests that the rs11614913 polymorphism does not affect the mature miRNA expression, but shows its effect through target gene HOXC8 expression in glioma.
Similar content being viewed by others
Reference
Abdel-Fattah R, Xiao A, Bomgardner D, Pease CS, Lopes M, Hussaini IM (2006) Differential expression of HOX genes in neoplastic and non-neoplastic human astrocytes. J Pathol 209(1):15–24
Adwan H, Zhivkova-Galunska M, Georges R, Eyol E, Kleeff J, Giese NA, Friess H, Bergmann F, Berger MR (2011) Expression of HOXC8 is inversely related to the progression and metastasis of pancreatic ductal adenocarcinoma. Br J Cancer 105(2):288–295
Akkız H, Bayram S, Bekar A, Akgöllü E, Ülger Y (2011) A functional polymorphism in pre-microRNA-196a-2 contributes to the susceptibility of hepatocellular carcinoma in a Turkish population: a case–control study. J Viral Hepat 18(7):e399–e407
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297
Chen KN, Gu ZD, Ke Y, Li JY, Shi XT, Xu GW (2005) Expression of 11 HOX genes is deregulated in esophageal squamous cell carcinoma. Clin Cancer Res 11(3):1044–1049
Christensen BC, Avissar-Whiting M, Ouellet LG, Butler RA, Nelson HH, McClean MD, Marsit CJ, Kelsey KT (2010) Mature microRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer. Clin Cancer Res 16(14):3713–3720
Dou T, Wu Q, Chen X, Ribas J, Ni X, Tang C, Huang F, Zhou L, Lu D (2010) A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population. J Cancer Res Clin Oncol 136(12):1853–1859
Du YB, Dong B, Shen LY, Yan WP, Dai L, Xiong HC, Liang Z, Kang XZ, Qin B, Chen KN (2014) The survival predictive significance of HOXC6 and HOXC8 in esophageal squamous cell carcinoma. J Surg Res 188(2):442–450
George GP, Gangwar R, Mandal RK, Sankhwar SN, Mittal RD (2011) Genetic variation in microRNA genes and prostate cancer risk in north Indian population. Mol Biol Rep 38(3):1609–1615
Goodenberger ML, Jenkins RB (2012) Genetics of adult glioma. Cancer genetics 205(12):613–621
Grier DG, Thompson A, Kwasniewska A, McGonigle GJ, Halliday HL, Lappin TR (2005) The pathophysiology of HOX genes and their role in cancer. J Pathol 205(2):154–171
Guan Y, Mizoguchi M, Yoshimoto K, Hata N, Shono T, Suzuki SO, Araki Y, Kuga D, Nakamizo A, Amano T, Ma X (2010) MiRNA-196 is upregulated in glioblastoma but not in anaplastic astrocytoma and has prognostic significance. Clin Cancer Res 16(16):4289–4297
Guan Y, Chen L, Bao Y, Qiu B, Pang C, Cui R, Wang Y (2015) High miR-196a and low miR-367 cooperatively correlate with unfavorable prognosis of high-grade glioma. International journal of clinical and experimental pathology 8(6):6576
Hoffman AE, Zheng T, Yi C, Leaderer D, Weidhaas J, Slack F, Zhang Y, Paranjape T, Zhu Y (2009) microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. Cancer Res 69(14):5970–5977
Hu Z, Chen J, Tian T et al (2008) Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest 118:2600–2608
Hu Z, Liang J, Wang Z, Tian T, Zhou X, Chen J, Miao R, Wang Y, Wang X, Shen H (2009) Common genetic variants in pre-microRNAs were associated with increased risk of breast cancer in Chinese women. Hum Mutat 30(1):79–84
Hu E, Wang D, Zhang X, Li J, Hu Y, Gong H, Liu E (2013) Four common polymorphisms in MicroRNAs and the risk of adult glioma in a Chinese case–control study. J Mol Neurosci 51(3):933–940
Jin Y, Lee CG (2013) Single nucleotide polymorphisms associated with microRNA regulation. Biomolecules 3(2):287–302
Karsy M, Arslan E, Moy F (2012) Current progress on understanding microRNAs in glioblastoma multiforme. Genes & cancer 3(1):3–15
Li Y, Zhang M, Chen H, Dong Z, Ganapathy V, Thangaraju M, Huang S (2010) Ratio of miR-196 s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. Cancer Res 70(20):7894–7904
Li M, Li J, Liu L, Li W, Yang Y, Yuan J (2013) MicroRNA in human glioma. Cancers 5(4):1306–1331
Li Y, Chao F, Huang B, Liu D, Kim J, Huang S (2014) HOXC8 promotes breast tumorigenesis by transcriptionally facilitating cadherin-11 expression. Oncotarget 5(9):2596
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathologica 114(2):97–109
Lu S, Liu R, Su M, Wei Y, Yang S, He S, Wang X, Qiang F, Chen C, Zhao S, Qian L (2016) Overexpression of HOXC8 is associated with poor prognosis in epithelial ovarian cancer. Reprod Sci. doi:10.1177/1933719115625845
Mueller DW, Bosserhoff AK (2011) MicroRNA miR-196a controls melanoma-associated genes by regulating HOX-C8 expression. Int J Cancer 129(5):1064–1074
Pencheva N, Tavazoie SF (2013) Control of metastatic progression by microRNA regulatory networks. Nat Cell Biol 15(6):546–554
Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8(1):23–36
Srivastava K, Srivastava A, Mittal B (2010) Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population. J Hum Genet 55(8):495–499
Tian T, Shu Y, Chen J, Hu Z, Xu L, Jin G, Liang J, Liu P, Zhou X, Miao R, Ma H (2009) A functional genetic variant in microRNA-196a2 is associated with increased susceptibility of lung cancer in Chinese. Cancer Epidemiol Biomark Prev 18(4):1183–1187
Xu P, Zhang X, Ni W, Fan H, Xu J, Chen Y, Zhu J, Gu X, Yang L, Ni R, Chen B (2015) Upregulated HOXC8 expression is associated with poor prognosis and Oxaliplatin resistance in hepatocellular carcinoma. Dig Dis Sci 60(11):3351–3363
Yang G, Han D, Chen X, Zhang D, Wang L, Shi C, Zhang W, Li C, Chen X, Liu H, Zhang D (2014) MiR-196a exerts its oncogenic effect in glioblastoma multiforme by inhibition of IκBα both in vitro and in vivo. Neuro-Oncology. doi:10.1093/neuonc/not307
Yekta S, Shih IH, Bartel DP (2004) MicroRNA-directed cleavage of HOXB8 mRNA. Science 304(5670):594–596
Yoon DJ, Kwan BH, Chao FC, Nicolaides TP, Phillips JJ, Lam GY, Mason AB, Weiss WA, Kamei DT (2010) Intratumoral therapy of glioblastoma multiforme using genetically engineered transferrin for drug delivery. Cancer Res 70(11):4520–4527
Zhan JF, Chen LH, Chen ZX, Yuan YW, Xie GZ, Sun AM, Liu Y (2011) A functional variant in microRNA-196a2 is associated with susceptibility of colorectal cancer in a Chinese population. Arch Med Res 42(2):144–148
Zhao H, Xu J, Zhao D, Geng M, Ge H, Fu L, Zhu Z (2016) Somatic mutation of the SNP rs11614913 and its association with increased MIR 196A2 expression in breast cancer. DNA Cell Biol 35(2):81–87
Acknowledgments
This study was financially supported by DST-SERB, Government of India, and project sanction No. SR/SO/HS/0233/2012. Histopathology diagnosis done by the Department of Neuropathology, NIMHANS, Bangalore is duly acknowledged.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors have declared that there is no conflict of interest financially or findings specified in this paper.
Additional information
Sibin M K and Harshitha S M have contributed equally.
Rights and permissions
About this article
Cite this article
Sibin, M.K., Harshitha, S.M., Narasingarao, K.V.L. et al. Effect of rs11614913 Polymorphism on Mature miR196a2 Expression and its Target Gene HOXC8 Expression in Human Glioma. J Mol Neurosci 61, 144–151 (2017). https://doi.org/10.1007/s12031-016-0855-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12031-016-0855-z