MicroRNA-106a-5p alleviated the resistance of cisplatin in lung cancer cells by targeting Jumonji domain containing 6.
摘要:
Cisplatin (DDP) is used for lung cancer therapy. MicroRNAs, small non-coding RNAs, may contribute to tumorigenesis as well as to drug resistance. We examined regulatory functions of miR-106a-5p in DDP-resistant lung cancer cells. Differentially expressed miRNAs were provided by Gene Expression Omnibus (GEO) datasets and RT-qPCR examined RNA levels of miR-106a-5p and Jumonji domain-containing protein 6 (JMJD6), an enzyme causing lysine hydroxylation and arginine demethylation. Bindings were determined by luciferase reporter assay. Additionally, the half maximal inhibitory concentration (IC50) of DDP was determined through Cell Counting Kit-8 (CCK-8) after treated by DDP (0, 6.25, 12.5, 25, 50 and 75 μM) and apoptosis rates were analyzed using flow cytometry. Besides that, migratory ability and invasiveness were examined by transwell. Western blot was for measuring protein levels of Bcl-2, Bax in apoptosis and E-cadherin, N-cadherin in epithelial-mesenchymal transition (EMT). The IC50 value of DDP-resistant A549 (A549/DDP) cells was higher, so were migration, invasion and N-cadherin in EMT while the apoptosis and E-cadherin in EMT were lower versus the parental A549 cells (no DDP resistance). MiR-106a-5p was low expressed in A549/DDP cells while its overexpression caused decreased migration, invasiveness and EMT but promoted apoptosis. JMJD6 was directly targeted and negatively regulated by miR-106a-5p. Inhibited JMJD6 decreased migratory ability, invasion and EMT but improved apoptosis. Moreover, knockdown of miR-106a-5p induced high level of JMJD6, migration, invasiveness and EMT but low apoptosis rates, which were restrained by JMJD6 suppression. MiR-106a-5p/JMJD6 axis accelerated cell apoptosis and suppressed invasiveness, migration and EMT in A549/DDP cells.
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DOI:
10.1016/j.trim.2021.101478
被引量:
年份:
1970


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