MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo.
Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs in our induced paclitaxel-resistant NPC CNE-1/Taxol cells. Furthermore, we clarified the role of miR-634, most significantly downregulated in the paclitaxel-resistant CNE-1/Taxol, in regulating the paclitaxel sensitivity in NPC cells. We restored miR-634 expression in the CNE-1/Taxol cells by lentivirus infection, and found restoration of miR-634 re-sensitized the CNE-1/Taxol cells to paclitaxel in vitro by MTT assay and colony formation assay. In xenograft mouse model, we found that miR-634 inhibited tumor growth and enhanced paclitaxel sensitivity. Thus, our findings provide important information for the development of targeted gene therapy for reversing paclitaxel resistance in NPC.
Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha 410013, Hunan, China.
Xiaowei
X
Peng
Department of Oncology, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Peiguo
P
Cao
Department of Respiratory, The Second People's Hospital of Hunan Province Changsha 410013, Hunan, China.
Dong
D
He
Department of Oncology, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Shuang
S
Han
Department of Plastic Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Jianda
J
Zhou
Department of Otolaryngology-Head and Neck Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Guolin
G
Tan
Department of Otolaryngology-Head and Neck Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Wei
W
Li
Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha 410013, Hunan, China.
Fenghui
F
Yu
Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha 410013, Hunan, China.
Jianjun
J
Yu
Department of Head and Neck Surgery, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University Changsha 410013, Hunan, China.
Zan
Z
Li
Department of Oncology, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Ke
K
Cao
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; C000599270:MIRN-634 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel
Microarray; nasopharyngeal carcinoma; paclitaxel resistance; targeted therapy