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

Zhanqin Zhang; Hongtao Zhu; Jianguo Hu

doi:10.1038/s41419-021-03486-1

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

Cell Death Dis. 2021 Feb 26;12(2):219. doi: 10.1038/s41419-021-03486-1.

Authors

Zhanqin Zhang¹, Hongtao Zhu², Jianguo Hu³

Affiliations

¹ Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
³ Department of Obstetrics and Gynecology, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China. angeljianguo@163.com.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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