Oncotarget

Research Papers:

The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and inhibits multi-chemoresistance in bladder cancer

Yang Li, Hui Deng, Lei Lv, Cheng Zhang, Liting Qian, Jun Xiao, Weidong Zhao, Qi Liu, Daming Zhang, Yingwei Wang, Jun Yan, Hongyu Zhang, Yinghua He and Jingde Zhu _

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Oncotarget. 2015; 6:10195-10206. https://doi.org/10.18632/oncotarget.3555

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Abstract

Yang Li1,*, Hui Deng2,*, Lei Lv2,*, Cheng Zhang3,*, Liting Qian4, Jun Xiao5, Weidong Zhao6, Qi Liu7, Daming Zhang8, Yingwei Wang9, Jun Yan3, Hongyu Zhang10, Yinghua He10 and Jingde Zhu2,10

1 Department of Biology, School of Life Science, Anhui Medical University, Hefei, Anhui, China

2 Cancer Epigenetics Program, Anhui Cancer Hospital, Hefei, Anhui, China

3 Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

4 Department of Radiotherapy, Anhui Cancer Hospital, Hefei, Anhui, China

5 Department of Urology, Anhui Provincial Hospital, Hefei, Anhui, China

6 Department of Gynecologic Cancer, Anhui Cancer Hospital, Hefei, Anhui, China

7 School of Life Science and Technology, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang, China

8 Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

9 Department of Pathology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

10 Cancer Epigenetics Program, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University, Shanghai, China

* These authors contributed equally to this work

Correspondence to:

Jingde Zhu, email:

Keywords: ING5, miR-193a-3p, chemoresistance, bladder cancer, protein acetylation

Received: February 12, 2015 Accepted: February 13, 2015 Published: March 12, 2015

Abstract

As the major barrier to curative cancer chemotherapy, chemoresistance presents a formidable challenge to both cancer researchers and clinicians. We have previously shown that the bladder cancer (BCa) cell line 5637 is significantly more sensitive to the cytoxicity of five chemotherapeutic agents than H-bc cells. Using an RNA-seq-based omic analysis and validation at both the mRNA and protein levels, we found that the inhibitor of growth 5 (ING5) gene was upregulated in 5637 cells compared with H-bc cells, indicating that it has an inhibitory role in BCa chemoresistance. siRNA-mediated inhibition of ING5 increased the chemoresistance and inhibited the DNA damage response pathway in 5637 cells. Conversely, forced expression of EGFP-ING5 decreased the chemoresistance of and activated the DNA damage response pathway in H-bc cells. We also showed that ING5 gene expression is inhibited by miR-193a-3p and is instrumental in miR-193a-3p’s role in activating BCa chemoresistance. Our results demonstrate both the role and mechanism of inhibition of BCa chemoresistance by ING5.


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