The miR-34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
BACKGROUND
Chemoresistance hinders the curative cancer chemotherapy. MicroRNAs (miRNAs) are key players in diverse biological processes including the chemoresistance of cancers.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Pu|Youguang|Y|', 'Zhao|Fangfang|F|', 'Li|Yinpeng|Y|', 'Cui|Mingda|M|', 'Wang|Haiyan|H|', 'Meng|Xianghui|X|', 'Cai|Shanbao|S|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D001859:Bone Neoplasms D049109:Cell Proliferation D002945:Cisplatin D015536:Down-Regulation D019008:Drug Resistance, Neoplasm D015972:Gene Expression Regulation, Neoplastic D006801:Humans D051379:Mice D008819:Mice, Nude D035683:MicroRNAs D012516:Osteosarcoma D034741:RNA, Small Interfering D044140:Receptor, Angiotensin, Type 1 D014407:Tumor Cells, Cultured D023041:Xenograft Model Antitumor Assays
miR-34a-5p Multi-chemoresistance Osteosarcoma AGTR1