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Updated: Oct 14, 2025

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma growth and metastasis
Wu Xing1, Peng-Cheng Zhou2,3, Hao-Ye Zhang2
1Department of Radiology, Xiangya Hospital, Central South University, Changsha, China.
Background & Aims:
Hepatocellular carcinoma (HCC) is one of the leading causes of tumour-related death. Here, we investigated the molecular mechanism of HCC by studying the function of circ_GLIS2.
Methods:
Human HCC specimens and cell lines were used. Sanger sequencing, actinomycin D and RNase R treatment were performed to validate circular RNA features of circ_GLIS2. qRT-PCR, western blotting, immunostaining, and IHC were employed to examine levels of circ_GLIS2, GLIS2 mRNA, and EMT-related markers. CCK-8, colony formation, flow cytometry, wound healing assay, and transwell assays were performed to evaluate cancer cell proliferation, apoptosis, migration, and invasion. RIP and RNA pull-down assay were used to validate EIF4A3/GLIS2 mRNA interaction. MSP was performed to measure the methylation status of GLIS2 promoter. Nude mouse xenograft model was used to examine tumour growth and metastasis in vivo.
Results:
Circ_GLIS2 and linear GLIS2 mRNA were reduced in human HCC tissues and cells. Their low levels correlated with a poor survival rate of HCC patients. Overexpression of circ_GLIS2 and GLIS2 suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis. GLIS2 promoter region was hypermethylated in HCC cells. EIF4A3 was directly bound with GLIS2 mRNA and promoted circ_GLIS2/GLIS2 expression. Moreover, overexpression of circ_GLIS2 restrained HCC tumour growth and metastasis in vivo.
Conclusion:
Circ_GLIS2 suppresses HCC growth and metastasis by inhibiting cell proliferation, migration, and invasion, but promoting cell apoptosis. These findings provide molecular insights into the mechanism of HCC and indicate that circ_GLIS2 could serve as a diagnosis marker or therapeutic target for HCC.
Insights
Circular RNA circ_GLIS2 suppresses hepatocellular carcinoma (HCC) growth and metastasis. Low circ_GLIS2 levels correlate with poor patient survival, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide.
- Understanding the molecular mechanisms underlying HCC progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the functional role of circ_GLIS2 in the molecular mechanisms of HCC.
- To explore the potential of circ_GLIS2 as a diagnostic marker or therapeutic target for HCC.
Main Methods:
- Analysis of circ_GLIS2 and GLIS2 mRNA levels in HCC tissues and cell lines.
- Functional assays (proliferation, apoptosis, migration, invasion) to assess the impact of circ_GLIS2.
- In vivo studies using a nude mouse xenograft model to evaluate tumor growth and metastasis.
Main Results:
- Circ_GLIS2 and GLIS2 mRNA were downregulated in HCC, correlating with poor patient survival.
- Overexpression of circ_GLIS2 inhibited HCC cell proliferation, migration, and invasion, while promoting apoptosis.
- Circ_GLIS2 overexpression suppressed tumor growth and metastasis in vivo.
Conclusions:
- Circ_GLIS2 acts as a tumor suppressor in HCC by inhibiting proliferation, migration, and invasion, and promoting apoptosis.
- Circ_GLIS2 represents a promising diagnostic marker and therapeutic target for hepatocellular carcinoma.
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