Circ_0098823 binding with IGF2BP3 regulates DNM1L stability to promote metastasis of hepatocellular carcinoma via mitochondrial fission.

Publisher: Springer Country of Publication: Netherlands NLM ID: 9712129 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-675X (Electronic) Linking ISSN: 13608185 NLM ISO Abbreviation: Apoptosis Subsets: MEDLINE

Publication: 2005- : Dordrecht, Netherlands : Springer
Original Publication: London : Rapid Science Publishers,

Carcinoma, Hepatocellular*/genetics ; Carcinoma, Hepatocellular*/pathology ; Carcinoma, Hepatocellular*/metabolism ; Liver Neoplasms*/genetics ; Liver Neoplasms*/pathology ; Liver Neoplasms*/metabolism ; RNA, Circular*/genetics ; RNA, Circular*/metabolism ; Mitochondrial Dynamics*/genetics ; RNA-Binding Proteins*/genetics ; RNA-Binding Proteins*/metabolism ; Dynamins*/genetics ; Dynamins*/metabolism ; Apoptosis*/genetics ; Cell Proliferation*/genetics ; Gene Expression Regulation, Neoplastic*; Humans ; Animals ; Mice ; Cell Line, Tumor ; Cell Movement/genetics ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; Male ; Neoplasm Metastasis ; Microtubule-Associated Proteins/genetics ; Microtubule-Associated Proteins/metabolism ; GTP Phosphohydrolases/genetics ; GTP Phosphohydrolases/metabolism ; Mice, Nude ; Mice, Inbred BALB C

Hepatocellular carcinoma (HCC) is highly metastatic and invasive. CircRNA participates in gene regulation of multiple tumor metastases, but little is known whether it is a bystander or an actual player in HCC metastasis. We aim to explore the molecular mechanisms of novel circRNAs in HCC metastasis. RT-qPCR was used to detect the expression of 13 circRNAs derived by the ERBB3 gene. The function of circ_0098823 and DNM1L in HCC cells were estimated by CCK-8, transwell assays, flow cytometry, electron microscope, and in vivo experiments. RNA binding protein of circ_0098823 was confirmed by RNA pull-down, mass spectrometry, and RNA immunoprecipitation. The expression of DNM1L after IGF2BP3 knockdown was detected by RT-qPCR and western blot. Circ_0098823 was significantly up-regulated both in HCC tissues and HGF induced cell lines. Circ_0098823 overexpression significantly enhanced proliferation, migration, and invasion but decreased apoptosis of HCC cells, particularly promoted mitochondrial fission. Compared with the control group, the tumors in the circ_0098823 knockdown mice were significantly smaller and lighter. Circ_0098823 silencing suppressed DNM1L expression, a key molecule for fission, which enhanced proliferation, migration and invasion, and inhibited apoptosis of HCC cell. IGF2BP3 was a binding protein of circ_0098823. The expression and mRNA stability of DNM1L were down-regulated by IGF2BP3 knockdown. IGF2BP3 knockdown significantly alleviated the excessive migration, invasion and apoptosis of HCC cells caused by circ_0098823 overexpression. This study uncovered a novel circ_0098823 with tumor-promoting effect, and the mechanism by which circ_0098823 participates in HCC progression through IGF2BP3-guided DNM1L. Our study broadens molecular understanding of HCC progression.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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82003117 National Natural Science Foundation of China

Keywords: Circ_0098823; DNM1L; ERBB3; Hepatocellular carcinoma; IGF2BP3; Mitochondrial fission

0 (RNA, Circular)
0 (RNA-Binding Proteins)
EC 3.6.5.5 (Dynamins)
EC 3.6.5.5 (DNM1L protein, human)
0 (IGF2BP3 protein, human)
0 (Mitochondrial Proteins)
0 (Microtubule-Associated Proteins)
EC 3.6.1.- (GTP Phosphohydrolases)

Date Created: 20240308 Date Completed: 20240427 Latest Revision: 20240507

20240508

10.1007/s10495-023-01903-8

38459420