Molecular Mechanism into CDR1as-Mediated miR-7 Sponging in the Regulation of Insulinoma Cell Proliferation and Apoptosis

Pancreatic neuroendocrine tumors (PNETs) are rare malignancies with incompletely understood molecular mechanisms. Emerging evidence implicates non-coding RNAs in tumorigenesis, including circular RNA ciRS-7, which functions as a competitive endogenous RNA by sponging miR-7—a known tumor suppressor. Here, we report that ciRS-7 is significantly upregulated, while miR-7 is downregulated, in the human insulinoma cell line NES2Y. Knockdown of ciRS-7 suppressed cell proliferation (assessed by CCK-8 and colony formation assays) and induced apoptosis (measured by flow cytometry), accompanied by increased expression of pro-apoptotic proteins Bax and Caspase-3. Conversely, ciRS-7 overexpression enhanced proliferative capacity and upregulated the miR-7 targets Myrip and Pax6. Mechanistic studies confirmed that ciRS-7 modulates Myrip and Pax6 expression via miR-7 sequestration. Notably, silencing Myrip reversed ciRS-7–mediated effects, inhibiting proliferation and promoting apoptosis. These findings demonstrate that ciRS-7 promotes insulinoma cell growth by acting as a miR-7 sponge and activating the Myrip/Pax6 signaling axis, highlighting its potential as a therapeutic target in PNETs.