title: Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET.
abstract: Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that up-regulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Zhandong
authors: Z
authors: Zhang
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Ye
authors: Y
authors: Kong
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Wei
authors: W
authors: Yang
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Fei
authors: F
authors: Ma
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Yonglei
authors: Y
authors: Zhang
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Sheqing
authors: S
authors: Ji
authors: Surgical Oncology, The People Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China.
authors: Er-Min
authors: EM
authors: Ma
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Hongxing
authors: H
authors: Liu
authors: Department of Radiotherapy, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Yongshun
authors: Y
authors: Chen
authors: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.
authors: Yawei
authors: Y
authors: Hua
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis* / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D002945:Cisplatin