Microrna-106a-3p Induces Apatinib Resistance And Activates Janus-Activated Kinase 2 (Jak2)/Signal Transducer And Activator Of Transcription 3 (Stat3) By Targeting The Socs System In Gastric Cancer

Background: MicroRNA (miR)-106a was involved in the tumorigenesis and highly expressed in gastric cancer. Required apa- tinib resistance greatly limits its efficacy in patients. Thus, the aim of the present study was to investigate the potential role of miR-106a-3p in gastric cancer cells with apatinib-resistance.Material/Methods: The expression of miR-106a-3p was quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8) assay was performed to analyze the sensitivity of gastric cancer cells to apatinib. The expression of relevant drug-resistant proteins was detected by western blot. We searched Targetscan6.2 to find out the target gene of miR-106a-3p. Luciferase reporter assay was used to analyze whether miR-106a-3p bound to relevant gene of SOCS family. The SOCS2, SOCS4, and SOCSS were qualified by western blot, and their mRNA levels were detected by RT-qPCR. Further, JAK2, STAT3, and their phosphorylation levels were detected by western blot.Results: The results showed that the expression of miR-106a-3p was increased in apatinib-resistant gastric cancer, while miR-106a-3p inhibitor reduced the drug-resistance of SGC-7901-AP cells to apatinib. Dual luciferase reporter gene assay suggested that SOCS2, SOCA, and SOCS5 were target genes of miR-106a-3p. The relevant SOCS genes silencing reversed the effects of miR-106a-3p inhibitor on decreasing the apatinib resistance of SGC-7901-AP cells, while the phosphorylation level of JAK and STAT reduced by miR-106a-3p inhibitor were increased.Conclusions: miR-106a-3p induces apatinib resistance and activates JAK2/STAT3 by targeting SOCS system in gastric cancer. miR-106a-3p/SOCS plays a potent role in gastric cancer cell resistance to apatinib.