CircRAB11FIP1 promoted autophagy flux of ovarian cancer through DSC1 and miR-129.

Abstract

At present, no systematic and in-depth study is available on the function and potential mechanisms of circular RNA in autophagy. This study aimed to screen the expression profiles of circRNA, miRNA, and mRNA of ovarian cancer cells induced by Torin 1 (10 µM). The expression profiles of circRNA, miRNA, and mRNA were analyzed with next-generation sequencing technology. CircRAB11FIP1 expression was elevated in epithelial ovarian cancer (EOC) tissues than in normal ovarian tissues. Silencing circRAB11FIP1 inhibited the autophagic flux of ovarian cancer SKOV3 cells. However, circRAB11FIP1 overexpression activated the autophagic flux of ovarian cancer A2780 cells. CircRAB11FIP1-induced autophagy accelerated EOC proliferation and invasion. Also, circRAB11FIP1 directly bound to miR-129 and regulated its targets ATG7 and ATG14. CircRAB11FIP1 bound to desmocollin 1to facilitate its interaction with ATG101. Also, circRAB11FIP1 directly bound to the mRNA of fat mass and obesity-associated protein and promoted its expression. Then, circRAB11FIP1 mediated mRNA expression levels of ATG5 and ATG7 depending on m6A. In general, this study demonstrated that circRAB11FIP1 regulated ATG7 and ATG14 by sponging miR-129. The data suggested that circRAB11FIP1 might serve as a candidate biomarker for EOC diagnosis and treatment.

• Authors: Zhanqin Zhang, Hongtao Zhu, Jianguo Hu
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 2 Pg. 219 (02 26 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 33637694 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
• ATG14 protein, human
• Adaptor Proteins, Vesicular Transport
• Autophagy-Related Proteins
• DSC1 protein, human
• Desmocollins
• MicroRNAs
• Mirn129 microRNA, human
• Naphthyridines
• Protein Kinase Inhibitors
• RNA, Circular
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO
• FTO protein, human
• MTOR protein, human
• TOR Serine-Threonine Kinases
• Atg7 protein, human
• Autophagy-Related Protein 7

Topics

• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Alpha-Ketoglutarate-Dependent Dioxygenase FTO (genetics, metabolism)
• Animals
• Autophagy (drug effects)
• Autophagy-Related Protein 7 (genetics, metabolism)
• Autophagy-Related Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Desmocollins (genetics, metabolism)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Naphthyridines (pharmacology)
• Ovarian Neoplasms (drug therapy, genetics, metabolism, pathology)
• Protein Kinase Inhibitors (pharmacology)
• RNA, Circular (genetics, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (antagonists & inhibitors, metabolism)