miR-133a enhances the sensitivity of Hep-2 cells and vincristine-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.
The expression levels of the copper transporter P-type adenosine triphosphatase (ATP7B) are known correlate with tumor cell sensitivity to cisplatin. However, the mechanisms underlying cisplatin resistance remained poorly understood. Therefore, in the present study, we treated Hep-2 cells and in-house-developed vincristine-resistant Hep-2v cells with 50, 100, or 200 µM cisplatin and assessed cell viability after 24 or 48 h. Hep-2v cells were shown to be resistant to 50-200 µM cisplatin. Furthermore, using immunofluorescence staining and western blot analysis, we noted that ATP7B, but not copper-transporting ATPase 1 (ATP7A), expression was significantly increased in Hep-2v cells, and this increase was maintained at a higher level compared with Hep-2 cells. As ATP7B is a target of microRNA 133a (miR‑133a), the ability of miR‑133a to influence cisplatin sensitivity in Hep-2v cells was then assessed by CCK-8 assay. We noted that miR‑133a expression was lower in both Hep-2 and Hep-2v cells compared with epithelial NP69 cells. Following treatment with 50 µM cisplatin, in Hep-2v cells expressing exogenous miR‑133a we noted reduced ATP7B expression, and these cells had a significantly lower survival rate compared with the control. The present study demonstrates that miR‑133a enhances the sensitivity of multidrug-resistant Hep-2v cells to cisplatin by downregulating ATP7B expression.
Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Xurui
X
Wang
Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Wei
W
Zhu
Department of Otorhinolaryngology, Jilin Province Cancer Hospital, Changchun, Jilin 130012, P.R. China.
Xiaodong
X
Zhao
Department of Otolaryngology-Head and Neck Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Ping
P
Wang
D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D000073840:Copper-Transporting ATPases; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D015398:Signal Transduction; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D014750:Vincristine; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin