miR-193a-3p regulates the multi-drug resistance of bladder cancer by targeting the LOXL4 gene and the oxidative stress pathway.

Abstract

BACKGROUND:

Chemoresistance is a major obstacle to the curative cancer chemotherapy and presents one of the most formidable challenges in both research and management of cancer.

RESULTS:

From the detailed studies of a multi-chemosensitive (5637) versus a chemoresistant (H-bc) bladder cancer cell lines, we showed that miR-193a-3p [GenBank: NR_029710.1] promotes the multi-chemoresistance of bladder cancer cells. We further demonstrated that lysyl oxidase-like 4 (LOXL4) gene [GenBank: NM_032211.6] is a direct target of miR-193a-3p and executes the former's impact on bladder cancer chemoresistance. The Oxidative Stress pathway activity is drastically affected by a forced reversal of miR-193a-3p or LOXL4 levels in cell and may act at the downstream of LOXL4 gene to relay the miR-193a-3p's impact on the multi-chemoresistance in both cultured cells and the tumor xenografts in nude mice.

CONCLUSIONS:

In addition to a new mechanistic insight, our results provide a set of the essential genes in this newly identified miR-193a-3p/LOXL4/Oxidative Stress axis as the diagnostic targets for a guided anti-bladder cancer chemotherapy.

• Authors: Hui Deng, Lei Lv, Yang Li, Cheng Zhang, Fang Meng, Youguang Pu, Jun Xiao, Liting Qian, Weidong Zhao, Qi Liu, Daming Zhang, Yingwei Wang, Hongyu Zhang, Yinghua He, Jingde Zhu
• Journal: Molecular cancer (Mol Cancer) Vol. 13 Pg. 234 (Oct 14 2014) ISSN: 1476-4598 [Electronic] England
• PMID: 25311867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN193 microRNA, human
• MicroRNAs
• Nuclear Proteins
• RNA, Messenger
• RNA, Small Interfering
• Ribonucleoproteins
• SRSF2 protein, human
• Serine-Arginine Splicing Factors
• Amino Acid Oxidoreductases
• LOXL4 protein, human
• Protein-Lysine 6-Oxidase
• Paclitaxel

Topics

• Amino Acid Oxidoreductases (genetics, metabolism)
• Animals
• Cell Line, Tumor
• Drug Resistance, Multiple (drug effects, genetics)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Models, Biological
• Nuclear Proteins (metabolism)
• Oxidative Stress (drug effects, genetics)
• Paclitaxel (pharmacology)
• Protein-Lysine 6-Oxidase
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (metabolism)
• Reproducibility of Results
• Ribonucleoproteins (metabolism)
• Serine-Arginine Splicing Factors
• Signal Transduction (drug effects, genetics)
• Urinary Bladder Neoplasms (genetics)
• Xenograft Model Antitumor Assays