title: The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
abstract: Chemoresistance hinders the curative cancer chemotherapy. MicroRNAs (miRNAs) are key players in diverse biological processes including the chemoresistance of cancers.
  
  
  
  A RNA-seq-based miR-omic analysis of osteosarcoma (OS) cells was performed to detect the levels of miR-34a-5p. Bioinformatics analysis revealed that AGTR1 is one of the target genes of miR-34a-5p. The mRNA and protein levels of AGTR1 were detected in both the miR-34a-5p-mimic transfected G-292 and miR-34a-5p-antagomiR transfected SJSA-1 cells. The involvement of AGTR1 with OS chemoresistance was validated by the experiments with siRNA-mediated repression or overexpression of the AGTR1 gene.
  
  
  
  We showed that miR-34a-5p promotes the multi- chemoresistance of OS. The angiotensin II type 1 receptor (AGTR1) gene, is one of the targets of miR-34a-5p in OS and thus negatively correlates with OS chemoresistance by systematic investigations of a multi-drug sensitive (G-292) and resistant (SJSA-1) OS cell lines. Down-regulation of the AGTR1 expression by siRNA passivates G-292 cells and suppresses cell apoptosis, while over-expression of AGTR1 sensitizes SJSA-1 cells and thus promotes the drug-triggered cell death.
  
  
  
  The miR-34a-5p and its target gene AGTR1 are the potential targets for an effective chemotherapy of OS. Our results also provide novel insights into the effective chemotherapy for OS patients.
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West Branch of Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West Branch of Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Xinxiang Medical University, Xinxiang, Henan, 453000, China.
authors.forename: Yinpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Xinxiang Medical University, Xinxiang, Henan, 453000, China.
authors.forename: Mingda
authors.initials: M
authors.lastname: Cui
authors.affiliation: Department of Clinical Geriatrics, Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedic Surgery, Anhui Cancer Hospital, West Branch of Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China.
authors.forename: Xianghui
authors.initials: X
authors.lastname: Meng
authors.affiliation: Cancer Epigenetics Program, Anhui Cancer Hospital, West Branch of Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China. sbc651116@163.com.|Xinxiang Medical University, Xinxiang, Henan, 453000, China. sbc651116@163.com.|Department of Orthopedic Surgery, Anhui Cancer Hospital, West Branch of Anhui Provincial Hospital, Anhui Medical University, Hefei, 230031, Anhui, China. sbc651116@163.com.
authors.forename: Shanbao
authors.initials: S
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C544065:AGTR1 protein, human; D000970:Antineoplastic Agents; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D002945:Cisplatin
keywords: AGTR1; Multi-chemoresistance; Osteosarcoma; miR-34a-5p