Deregulation of circRNA hsa_circ_0009109 promotes tumor growth and initiates autophagy by sponging miR-544a-3p in gastric cancer

Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs, which promotes tumor progression to a certain extent. Increasing reports have demonstrated the regulatory role of circular RNAs (circRNAs) in autophagy. Here, we aimed to determine the role of hsa_circ_0009109 in autophagy in gastric cancer (GC).

The hsa_circ_0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis, which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC.

The effects of hsa_circ_0009109 on autophagy were examined using quantitative real-time polymerase chain reaction (qPCR), transmission electron microscopy, Western blot, and immunofluorescence. The mechanism of hsa_circ_0009109 regulating the miR-544a-3p/bcl-2 axis was analysed using fluorescence in situ hybridization, dual-luciferase reporter, and rescue experiments.

Functional testing indicated that hsa_circ_0009109 was significantly down-expressed in GC tissues and cell lines. A reduction in cytoplasmic-derived hsa_circ_0009109 could promote GC progression by accelerating cell proliferation, enhancing migration and invasion, inhibiting apoptosis, and accelerating the cell cycle progression. Besides, hsa_circ_0009109 was found to exert the effect of an autophagy inhibitor such as 3-Methyladenine (3-MA), which was manifested by the weakening of the immunofluorescence of LC3B and the reduction in autophagy-related proteins after overexpression of hsa_circ_0009109, while increased autophagosomes were observed after interference with hsa_circ_0009109. Subsequently, the crosstalk between hsa_circ_0009109 and miR-544a-3p/bcl-2 was verified using dual-luciferase reporter assay. The autophagy status was altered under the regulation of the hsa_circ_0009109-targeted miR-544a-3p/bcl-2 axis. Conclusions: The hsa_circ_0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis, which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC.