Skip to main content

Advertisement

SpringerLink
Log in

MiR-212-3p inhibits cell proliferation and promotes apoptosis by targeting nuclear factor IA in bladder cancer

  • Published:
Journal of Biosciences Aims and scope Submit manuscript

Abstract

Accumulating evidence suggest that microRNAs play crucial roles in the development and progression of bladder cancer (BC). Here, we found that miR-212-3p was significantly down-regulated and negatively correlated with nuclear factor IA (NFIA) in human BC tissues. Bioinformatics analysis predicted that NFIA was a target gene of miR-212-3p. Then BC cell lines, T24 and J82 cells were transfected with miR-212-3p mimics or siNFIA to obtain miR-212-3p overexpression or NFIA knockdown cell lines, respectively. Quantitative real-time PCR was used to determine the expression of miR-212-3p and NFIA. Western blot analysis was utilized to detect NFIA expression. MTT assay showed either miR-212-3 overexpression or NFIA knockdown significantly inhibited the BC cell proliferation. Double staining with Annexin V-APC and 7-AAD showed the total number of apoptotic BC cells were remarkably increased after miR-212-3p overexpression or NFIA knockdown. Collectively, our results indicated that miR-212-3p targeting NFIA might serve as a promising target for BC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Al-Ahmadie HA, Iyer G, Lee BH, Scott SN, Mehra R, Bagrodia A, Jordan EJ, Gao SP, Ramirez R, Cha EK, Desai NB, Zabor EC, Ostrovnaya I, Gopalan A, Chen YB, Fine SW, Tickoo SK, Gandhi A, Hreiki J, Viale A, Arcila ME, Dalbagni G, Rosenberg JE, Bochner BH, Bajorin DF, Berger MF, Reuter VE, Taylor BS and Solit DB 2016 Frequent somatic CDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. Nat. Genet. 48 356–358

    Article  CAS  Google Scholar 

  • Antoni S, Ferlay J, Soerjomataram I, Znaor A, Jemal A and Bray F 2017 Bladder cancer incidence and mortality: A global overview and recent trends. Eur. Urol. 71 96–108

    Article  Google Scholar 

  • Bernard F, Gelsi-Boyer V, Murati A, Giraudier S, Trouplin V, Adelaide J, Rey J, Olschwang S, Vainchenker W, Chaffanet M, Vey N, Mozziconacci MJ and Birnbaum D 2009 Alterations of NFIA in chronic malignant myeloid diseases. Leukemia 23 583–585

    Article  CAS  Google Scholar 

  • Chen Y, Gao DY and Huang L 2015 In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv. Drug Deliv. Rev. 81 128–141

    Article  CAS  Google Scholar 

  • Chiyomaru T, Seki N, Inoguchi S, Ishihara T, Mataki H, Matsushita R, Goto Y, Nishikawa R, Tatarano S, Itesako T, Nakagawa M and Enokida H 2015 Dual regulation of receptor tyrosine kinase genes EGFR and c-Met by the tumor-suppressive microRNA-23b/27b cluster in bladder cancer. Int. J. Oncol. 46 487–496

    Article  CAS  Google Scholar 

  • Fu W, Tao T, Qi M, Wang L, Hu J, Li X, Xing N, Du R and Han B 2016 MicroRNA-132/212 upregulation inhibits TGF-beta-mediated epithelial-mesenchymal transition of prostate cancer cells by targeting SOX4. Prostate 76 1560–1570

    Article  CAS  Google Scholar 

  • Hansen KF, Sakamoto K, Aten S, Snider KH, Loeser J, Hesse AM, Page CE, Pelz C, Arthur JS, Impey S and Obrietan K 2016 Targeted deletion of miR-132/-212 impairs memory and alters the hippocampal transcriptome. Learn. Mem. 23 61–71

    Article  CAS  Google Scholar 

  • Hiraike Y, Waki H, Yu J, Nakamura M, Miyake K, Nagano G, Nakaki R, Suzuki K, Kobayashi H and Yamamoto S 2017 NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program. Nat. Cell Biol. 19 1081–1092

    Article  CAS  Google Scholar 

  • Hou P, Kang Y and Luo J 2018 Hypoxia-mediated miR-212-3p downregulation enhances progression of intrahepatic cholangiocarcinoma through upregulation of Rab1a. Cancer Biol. Ther. 1–10

  • Jin H, Sun W, Zhang Y, Yan H, Liufu H, Wang S, Chen C, Gu J, Hua X, Zhou L, Jiang G, Rao D, Xie Q, Huang H and Huang C 2018 MicroRNA-411 downregulation enhances tumor growth by upregulating MLLT11 expression in human bladder cancer. Mol. Ther. Nucleic. Acids. 11 312–322

    Article  CAS  Google Scholar 

  • Kamat AM, Hahn NM, Efstathiou JA, Lerner SP, Malmström P-U, Choi W, Guo CC, Lotan Y and Kassouf W 2016 Bladder cancer. Lancet 388 2796–2810

    Article  Google Scholar 

  • Kang CM, Hu YW, Nie Y, Zhao JY, Li SF, Chu S, Li HX, Huang QS and Qiu YR 2016 Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells. Mol. Med. Rep. 14 5288–5296

    Article  CAS  Google Scholar 

  • Lee JS, Xiao J, Patel P, Schade J, Wang J, Deneen B, Erdreich-Epstein A and Song HR 2014 A novel tumor-promoting role for nuclear factor IA in glioblastomas is mediated through negative regulation of p53, p21, and PAI1. Neuro Oncol 16 191–203

    Article  CAS  Google Scholar 

  • Lee J, Hoxha E and Song HR 2017 A novel NFIA-NFkappaB feed-forward loop contributes to glioblastoma cell survival. Neuro Oncol 19 524–534

    CAS  PubMed  Google Scholar 

  • Lewis BP, Burge CB and Bartel DP 2005 Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120 15–20

    Article  CAS  Google Scholar 

  • Lin S and Gregory RI 2015 MicroRNA biogenesis pathways in cancer. Nat. Rev. Cancer 15 321–333

    Article  CAS  Google Scholar 

  • Liu H, Li C, Shen C, Yin F, Wang K, Liu Y, Zheng B, Zhang W, Hou X, Chen X, Wu J, Wang X, Zhong C, Zhang J, Shi H, Ai J and Zhao S 2015 MiR-212-3p inhibits glioblastoma cell proliferation by targeting SGK3. J. Neurooncol. 122 431–439

    Article  CAS  Google Scholar 

  • Livak KJ and Schmittgen TD 2001 Analysis of relative gene expression data using real-time quantitative PCR and the 2 −ΔΔ C T method. Methods–A Companion Method Enzymol. 25 402–408

  • Matsushita R, Seki N, Chiyomaru T, Inoguchi S, Ishihara T, Goto Y, Nishikawa R, Mataki H, Tatarano S, Itesako T, Nakagawa M and Enokida H 2015 Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer. Br. J. Cancer 113 282–289

    Article  CAS  Google Scholar 

  • Matsushita R, Yoshino H, Enokida H, Goto Y, Miyamoto K, Yonemori M, Inoguchi S, Nakagawa M and Seki N 2016 Regulation of UHRF1 by dual-strand tumor-suppressor microRNA-145 (miR-145-5p and miR-145-3p): Inhibition of bladder cancer cell aggressiveness. Oncotarget. 7 28460–28487

    Article  Google Scholar 

  • Messina G, Biressi S, Monteverde S, Magli A, Cassano M, Perani L, Roncaglia E, Tagliafico E, Starnes L, Campbell CE, Grossi M, Goldhamer DJ, Gronostajski RM and Cossu G 2010 Nfix regulates fetal-specific transcription in developing skeletal muscle. Cell 140 554–566

    Article  CAS  Google Scholar 

  • Ramalinga M, Roy A, Srivastava A, Bhattarai A, Harish V, Suy S, Collins S and Kumar D 2015 MicroRNA-212 negatively regulates starvation induced autophagy in prostate cancer cells by inhibiting SIRT1 and is a modulator of angiogenesis and cellular senescence. Oncotarget. 6 34446–34457

    Article  Google Scholar 

  • Rupaimoole R and Slack FJ 2017 MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discovery 16 203–222

    Article  CAS  Google Scholar 

  • Semenova EA, Kwon MC, Monkhorst K, Song JY, Bhaskaran R, Krijgsman O, Kuilman T, Peters D, Buikhuisen WA, Smit EF, Pritchard C, Cozijnsen M, van der Vliet J, Zevenhoven J, Lambooij JP, Proost N, van Montfort E, Velds A, Huijbers IJ and Berns A 2016 Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients. Cell. Rep. 16 631–643

    Article  CAS  Google Scholar 

  • Tu H, Wei G, Cai Q, Chen X, Sun Z, Cheng C, Zhang L, Feng Y, Zhou H, Zhou B and Zeng T 2015 MicroRNA-212 inhibits hepatocellular carcinoma cell proliferation and induces apoptosis by targeting FOXA1. Onco. Targets Ther. 8 2227–2235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wada R, Akiyama Y, Hashimoto Y, Fukamachi H and Yuasa Y 2010 miR-212 is downregulated and suppresses methyl-CpG-binding protein MeCP2 in human gastric cancer. Int. J. Cancer 127 1106–1114

    Article  CAS  Google Scholar 

  • Wu R, Li F, Zhu J, Tang R, Qi Q, Zhou X, Li R, Wang W, Hua D and Chen W 2014 A functional variant at miR-132-3p, miR-212-3p, and miR-361-5p binding site in CD80 gene alters susceptibility to gastric cancer in a Chinese Han population. Med. Oncol. 31 60

    Article  Google Scholar 

  • Xie C, Chen B, Wu B, Guo J and Cao Y 2018 LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis. Biomed. Pharmacother. 97 1645–1653

    Article  CAS  Google Scholar 

  • Yang B, Zhou ZH, Chen L, Cui X, Hou JY, Fan KJ, Han SH, Li P, Yi SQ and Liu Y 2018 Prognostic significance of NFIA and NFIB in esophageal squamous carcinoma and esophagogastric junction adenocarcinoma. Cancer. Med. 7 1756–1765

    Article  CAS  Google Scholar 

  • Zhao J, Qiao CR, Ding Z, Sheng YL, Li XN, Yang Y, Zhu DY, Zhang CY, Liu DL, Wu K and Zhao S 2017 A novel pathway in NSCLC cells: miR191, targeting NFIA, is induced by chronic hypoxia, and promotes cell proliferation and migration. Mol. Med. Rep. 15 1319–1325

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, the First Hospital of Jiaxing, Jiaxing, Zhejiang Province, People’s Republic of China

    Xiaoming Wu, Hao Chen, Gaoyue Zhang, Jianhui Wu, Wei Zhu, Yanqin Gu & Yi He

Authors
  1. Xiaoming Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gaoyue Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jianhui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yanqin Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yi He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi He.

Additional information

Corresponding editor: Rita Mulherkar

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, X., Chen, H., Zhang, G. et al. MiR-212-3p inhibits cell proliferation and promotes apoptosis by targeting nuclear factor IA in bladder cancer. J Biosci 44, 80 (2019). https://doi.org/10.1007/s12038-019-9903-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12038-019-9903-5

Keywords

Search

Navigation