Circ_0078607 increases platinum drug sensitivity via miR-196b-5p/GAS7 axis in ovarian cancer

Abstract

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms. Circ_0078607, miR-196b-5p, and growth arrest-specific 7 (GAS7) levels were assessed by qPCR. Circ_0078607 stability was assessed by ribonuclease R digestion and actinomycin D treatment. Cell viability of various conic of DDP treatment was measured by CCK-8. The cell proliferation was determined by CCK-8 and colony formation assay. Western blotting was performed for determining GAS7, ABCB1, CyclinD1 and Bcl-2 protein levels. The direct binding between miR-196b-5p and circ_0078607 or GAS7 was validated by dual-luciferase reporter and RIP assay. DDP resistance in vivo was evaluated in nude mice. Immunohistochemistry staining for detecting Ki67 expression in xenograft tumours. Circ_0078607 and GAS7 was down-regulated, but miR-196b-5p was up-regulated in OC samples and DDP-resistant cells. Overexpression of circ_0078607 inhibited DDP resistance, cell growth and induced apoptosis in DDP-resistant OC cells. Mechanistically, circ_0078607 sequestered miR-196b-5p to up-regulate GAS7. MiR-196b-5p mimics reversed circ_0078607 or GAS7 overexpression-mediated enhanced sensitivity. Finally, circ_0078607 improved the sensitivity of DDP in vivo . Circ_0078607 attenuates DDP resistance via miR-196b-5p/GAS7 axis, which highlights the therapeutic potential of circ_0078607 to counter DDP resistance in OC.

The emerging role of circular RNAs in cisplatin resistance in ovarian cancer: From molecular mechanism to future potential

“…Circ_0078607 overexpression sequesters miR-196b-5p and regulates GAS7 expression, which functions as a targeted cell arrest gene. As a result, overexpression of circ_0078607 sensitizes OC cells to DPP [ 103 ]. In the following section, we discussed in detail a variety of circRNAs involved in OC and the regulatory mechanisms of their effective signaling pathways on DDP chemo-resistance.…”

The role of circRNAs in regulation of drug resistance in ovarian cancer

“…Furthermore, circ_0078607 was reported to inhibit tumor progression via governing the miR-32-5p and SIK1 pathways in ovarian cancer ( Jin and Wang, 2022 ). Circ_0078607 enhanced cisplatin sensitivity in ovarian cancer cells by regulation of miR-196b-5p and GAS7 (growth arrest-specific 7) expressions ( Dai et al, 2023 ). Circ_0078607 expression was lower in DDP-resistant ovarian cancer cells.…”

“…Upregulation of circ_0078607 suppressed cisplatin resistance, enhanced apoptosis and repressed cell proliferation in DDP-resistant cells. In term of mechanism, circ_0078607 sequestered miR-196b-5p and elevated the expression of GAS7 ( Dai et al, 2023 ). Therefore, circ_0078607 attenuated cisplatin resistance in ovarian cancer.…”

Targeting z-Crystallin by aspirin restores the sensitivity to cisplatin in resistant A2780 ovarian cancer cells

“…Even today, the mechanisms responsible for resistance in ovarian cancer treatment are poorly understood [1]. Regarding acquired resistance, the deregulation of anti-apoptotic genes Bcl-2 and Bcl-xL has been well established [2,3]. Expression of both genes is regulated by posttranscriptional mechanisms, including the interactions between stabilizing or destabilizing RNA-binding proteins (RBP) and their mRNAs [4].…”