Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People's Republic of China.
Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College, Nanchong, People's Republic of China.
Cancer Rep (Hoboken). 2024 Sep;7(9):e2128. doi: 10.1002/cnr2.2128.
CircRNAs and autophagy are closely involved in the physiological and pathological processes of ovarian cancer; however, their exact mechanisms are still undetermined. This investigation aimed to elucidate the function and associated pathways of circFAM188A, which modulates proliferation, autophagy, and invasion in ovarian cancer (EOC).
The expression of circFAM188A in the tissues of EOC patients was assessed via RT-PCR. To elucidate proliferation, invasion, and autophagy in the tumor cells, Transwell, 5-ethynyl-2'-deoxyuridine (EdU), and mRFP-GFP-LC3 reporter assays were conducted. The binding sites between circ-FAM188A and the miR-670-3p, miR-670-3p and YY1 were predicted using bioinformatics and verified by dual-luciferase reporter assays. Pulldown assays demonstrated binding between ULK1 and circ-FAM188A. ULK1 was found to be crucial in the initial stage of autophagy. Moreover, an in vivo xenograft model was established by subcutaneous injection of nude mice with EOC cells.
Expression of circ-FAM188A was increased in EOC tissues relative to normal ovarian tissues and circ-FAM188A overexpression promoted proliferation, invasion, and autophagy; these effects were reversed by circ-FAM188A silencing. miR-670-3p and circ-FAM188A co-localized in the cytoplasm. circ-FAM188A enhanced YY1 expression by sponging miR-670-3p and was also shown to interact with ULK1.
It is thus suggested that circ-FAM188A modulates autophagy by sponging miR-670-3p as well as interacting with ULK1.
CircRNAs 和自噬在卵巢癌的生理和病理过程中密切相关；然而，其确切机制仍未确定。本研究旨在阐明 circFAM188A 的功能及其相关途径，circFAM188A 调节卵巢癌（EOC）中的增殖、自噬和侵袭。
通过 RT-PCR 评估 EOC 患者组织中 circFAM188A 的表达。为了阐明肿瘤细胞中的增殖、侵袭和自噬，进行了 Transwell、5-乙炔基-2'-脱氧尿苷（EdU）和 mRFP-GFP-LC3 报告基因检测。使用生物信息学预测 circ-FAM188A 与 miR-670-3p、miR-670-3p 和 YY1 之间的结合位点，并通过双荧光素酶报告基因检测进行验证。下拉实验证明了 ULK1 和 circ-FAM188A 之间的结合。发现 ULK1 在自噬的初始阶段至关重要。此外，通过将 EOC 细胞皮下注射到裸鼠中建立体内异种移植模型。
circ-FAM188A 在 EOC 组织中的表达高于正常卵巢组织，circ-FAM188A 过表达促进增殖、侵袭和自噬；circ-FAM188A 沉默可逆转这些作用。miR-670-3p 和 circ-FAM188A 在细胞质中共定位。circ-FAM188A 通过海绵吸附 miR-670-3p 增强 YY1 表达，并且还与 ULK1 相互作用。
因此，circ-FAM188A 通过海绵吸附 miR-670-3p 以及与 ULK1 相互作用来调节自噬。
