Abstract
MicroRNAs play important roles in the pathogenesis of human diseases by regulating target gene expression in specific cells or tissues. Previously, we identified microRNA 452 (MIR452), which was specifically upregulated in early stage of human colorectal cancer (CRC) tissues. Here, we show the biological role of MIR452 and general transcription factor IIE subunit 1 (GTF2E1) in colorectal cancer. A luciferase reporter system was used to confirm the effect of MIR452 on GTF2E1 expression. The expression levels of MIR452 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR) and western blotting. We verified the association between MIR452 and the GTF2E1 expression and found that GTF2E1 transcripts were directly downregulated by MIR452. The mRNA and protein levels of GTF2E1 were also downregulated in CRC cells upon transfection with MIR452. GTF2E1 protein expression was decreased in CRC tissues compared to adjacent nontumour tissues. These results suggest that MIR452 might directly or indirectly regulate the genes transcription related to CRC by downregulating GTF2E1 expression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alam K. J., Mo J. S., Han S. H., Park W. C., Kim H. S., Yun K. J. et al. 2017 MicroRNA 375 regulates proliferation and migration of colon cancer cells by suppressing the CTGF-EGFR signaling pathway. Int. J. Cancer 141, 1614–1629.
Aydin Y., Kurt R., Song K., Lin D., Osman H., Youngquist B. et al. 2019 Hepatic stress response in HCV infection promotes STAT3-mediated inhibition of HNF4A-miR-122 feedback loop in liver fibrosis and cancer progression. Cancers (basel) 11, 10.
Bartel D. P. 2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297.
Bentley D. L. 2014 Coupling mRNA processing with transcription in time and space. Nat. Rev. Genet. 15, 163–175.
Braga E. A., Fridman M. V., Loginov V. I., Dmitriev A. A. and Morozov S. G. 2019 Molecular mechanisms in clear cell renal cell carcinoma: role of miRNAs and hypermethylated miRNA genes in crucial oncogenic pathways and processes. Front. Genet. 10, 320.
Brennecke J., Hipfner D. R., Stark A., Russell R. B. and Cohen S. M. 2003 bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113, 25–36.
Chang Z., Miao X. and Zhao W. 2020 Identification of prognostic dosage-sensitive genes in colorectal cancer based on multi-omics. Front. Genet. 10, 1310.
Chen X. L., Hong L. L., Wang K. L., Liu X., Wang J. L., Lei L. et al. 2019 Deregulation of CSMD1 targeted by microRNA-10b drives gastric cancer progression through the NF-κB pathway. Int. J. Biol. Sci. 15, 2075–2086.
Compe E., Genes C. M., Braun C., Coin F. and Egly J. M. 2019 TFIIE orchestrates the recruitment of the TFIIH kinase module at promoter before release during transcription. Nat. Commun. 7, 2084.
Garzon R., Fabbri M., Cimmino A., Calin G. A. and Croce C. M. 2006 MicroRNA expression and function in cancer. Trends Mol. Med. 12, 580–587.
Han S. H., Mo J. S., Park W. C. and Chae S. C. 2019 Reduced microRNA 375 in colorectal cancer upregulates metadherin-mediated signaling. World J. Gastroenterol. 25, 6495–6507.
Lu J., Getz G., Miska E. A., Alvarez-Saavedra E., Lamb J., Peck D. et al. 2005 MicroRNA expression profiles classify human cancers. Nature 435, 834–838.
Lu Z., Li X., Xu Y., Chen M., Chen W., Chen T. et al. 2019 microRNA-17 functions as an oncogene by downregulating Smad3 expression in hepatocellular carcinoma. Cell Death Dis. 10, 723.
Ma L., Teruya-Feldstein J. and Weinberg R. A. 2007 Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682–688.
Mo J. S. and Chae S. C. 2021 MicroRNA 452 regulates ASB8, NOL8, and CDR2 expression in colorectal cancer cells. Genes Genomics 43, 33–41.
Mo J. S., Alam K. J., Kang I. H., Park W. C., Seo G. S., Choi S. C. et al. 2015 MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells. Oncotarget 6, 2843–2855.
Mo J. S., Alam K. J., Kim H. S., Lee Y. M., Yun K. J. and Chae S. C. 2016 MicroRNA 429 regulates mucin gene expression and secretion in murine model of colitis. J. Crohns Colitis 10, 850–859.
Mo J. S., Park W. C., Choi S. C., Yun K. J. and Chae S. C. 2019 MicroRNA 452 regulates cell proliferation, cell migration, and angiogenesis in colorectal cancer by suppressing VEGFA expression. Cancers 11, 1613.
Ohkuma Y., Sumimoto H., Horikoshi M. and Roeder R. G. 1990 Factors involved in specific transcription by mammalian RNA polymerase II: purification and characterization of general transcription factor TFIIE. Proc. Natl. Acad. Sci. USA 87, 9163–9167.
Okamoto T., Yamamoto S., Watanabe Y., Ohta T., Hanaoka F., Roeder R. G. et al. 1998 Analysis of the role of TFIIE in transcriptional regulation through structure function studies of the TFIIEb subunit. J. Biol. Chem. 273, 19866–19876.
Orphanides G., Lagrange T. and Reinberg D. 1996 The general transcription factors of RNA polymerase II. Genes Dev. 10, 2657–2683.
Peterson M. G., Inostroza J., Maxon M. E., Flores O., Admon A., Reinberg D. et al. 1991 Structure and functional properties of human general transcription factor IIE. Nature 354, 369–373.
Roeder R. G. 1996 The role of general initiation factors in transcription by RNA polymerase II. Trends Biochem. Sci. 21, 327–335.
Serocki M., Bartoszewska S., Janaszak-Jasiecka A., Ochocka R. J., Collawn J. F. and Bartoszewski R. 2018 miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target. Angiogenesis 21, 183–202.
Su H., Yang J. R., Xu T., Huang J., Xu L., Yuan Y. et al. 2009 MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 69, 1135–1142.
Wang Y., Toh H. C., Chow P., Chung A. Y. F., Meyers D. J., Cole P. A. et al. 2012 MicroRNA-224 is upregulated in hepatocellular carcinoma through epigenetic mechanisms. Faseb. J. 26, 3032–3041.
Wang Y. F., Ao X., Liu Y., Ding D., Jiao W. J., Yu Z. et al. 2019 MicroRNA-608 promotes apoptosis in non-small cell lung cancer cells treated with doxorubicin through the inhibition of TFAP4. Front. Genet. 10, 809.
Watanabe T., Hayashi K., Tanaka A., Furumoto T., Hanaoka F. and Ohkuma Y. 2003 The carboxy terminus of the small subunit of TFIIE regulates the transition from transcription initiation to elongation by RNA polymerase II. Mol. Cell. Biol. 23, 2914–2926.
Zhang W. C., Wells J. M., Chow K. H., Huang H., Yuan M., Saxena T. et al. 2019a miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma. Nat. Metab. 1, 460–474.
Zhang Z., Pi J., Zou D., Wang X., Xu J., Yu S. et al. 2019b microRNA arm-imbalance in part from complementary targets mediated decay promotes gastric cancer progression. Nat. Commun. 10, 4397.
Zheng Q., Sheng Q., Jiang C., Shu J., Chen J., Nie Z. et al. 2014 MicroRNA-452 promotes tumorigenesis in hepatocellular carcinoma by targeting cyclin-dependent kinase inhibitor 1B. Mol. Cell. Biochem. 389, 187–195.
Acknowledgements
The biospecimens for this study were provided by the Biobank of Wonkwang University Hospital, a member of the National Biobank of Korea, which is supported by the Ministry of Health and Welfare. This research was supported by Wonkwang University in 2019.
Author information
Authors and Affiliations
Corresponding author
Additional information
Corresponding editor: Murali Dharan Bashyam
Rights and permissions
About this article
Cite this article
Mo, J.S., Chae, S.C. MicroRNA 452 regulates GTF2E1 expression in colorectal cancer cells. J Genet 100, 62 (2021). https://doi.org/10.1007/s12041-021-01312-3
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1007/s12041-021-01312-3