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Published on: October 4, 2019
The Inhibitory Effect of miR-345 on Glioma Progression Is Closely Related to circRNA-hsa_circ_0073237 and HDGF
Wu Xu1,2, Dan-Dan Che3, Qing Liu1
1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Glioma is the most common primary malignant tumor of the central nervous system and has a poor prognosis. Therefore, exploring the key molecular targets is a new opportunity for basic research and clinical treatment of glioma. Previous studies found that circRNA-hsa_circ_0073237 was upregulated in gliomas. Our further analyses of the biological function and molecular mechanism of hsa_circ_0073237 showed that hsa_circ_0073237 was also upregulated in glioma cell lines and could combine with miR-345 to inhibit its expression. miR-345 was downregulated in glioma tissues and cells, and targeted to regulate the expression of hepatoma-derived growth factor (HDGF), while HDGF expression was enhanced in glioma. Hsa_circ_0073237 promoted the expression of HDGF in glioma cells by adsorbing miR-345. Hsa_circ_0073237 siRNA, miR-345, and HDGF siRNA effectively inhibited cell viability and invasion and promoted cell apoptosis. When expression of hsa_circ_0073237 and miR-345 was inhibited simultaneously, cell viability, apoptosis, and invasion did not change significantly; however, after transfection with HDGF overexpression vector, the effects of hsa_circ_0073237 siRNA and miR-345 on glioma cell viability, apoptosis, and invasion were obviously reversed. Further construction of glioma xenograft models in nude mice confirmed that the introduction of miR-345 in vivo effectively inhibited tumor growth, significantly reduced tumor diameter and weight, and obviously decreased the expression of HDGF. Therefore, hsa_circ_0073237 can regulate the biological functions of glioma cells through miR-345/HDGF, thereby affecting the progression of tumors, indicating that the hsa_circ_0073237/miR-345/HDGF pathway may be a key target for the treatment of glioma.
Insights
Circular RNA hsa_circ_0073237 promotes glioma progression by sponging miR-345, leading to increased hepatoma-derived growth factor (HDGF) expression. Targeting this pathway offers a potential therapeutic strategy for glioma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Glioma, a common primary central nervous system malignancy, presents a poor prognosis, necessitating novel therapeutic targets.
- Previous research identified circRNA-hsa_circ_0073237 as upregulated in glioma tissues.
Purpose of the Study:
- To elucidate the biological function and molecular mechanism of circRNA-hsa_circ_0073237 in glioma.
- To investigate the role of the hsa_circ_0073237/miR-345/HDGF axis in glioma progression and its potential as a therapeutic target.
Main Methods:
- Analysis of circRNA-hsa_circ_0073237 and miR-345 expression in glioma cell lines and tissues.
- Investigation of the interaction between hsa_circ_0073237 and miR-345, and miR-345's regulation of HDGF.
- Functional assays (siRNA, overexpression vectors) assessing cell viability, invasion, and apoptosis in glioma cells.
- In vivo studies using glioma xenograft models in nude mice.
Main Results:
- Hsa_circ_0073237 was upregulated in glioma cells and inhibited miR-345 expression by acting as a molecular sponge.
- miR-345 was downregulated in glioma and targeted HDGF, whose expression was enhanced.
- Hsa_circ_0073237 promoted HDGF expression, enhancing glioma cell viability and invasion while inhibiting apoptosis; these effects were reversed by inhibiting hsa_circ_0073237 or miR-345, and exacerbated by HDGF overexpression.
- In vivo, miR-345 introduction inhibited tumor growth and HDGF expression.
Conclusions:
- The hsa_circ_0073237/miR-345/HDGF pathway significantly regulates glioma cell biological functions and tumor progression.
- This pathway represents a promising molecular target for the development of novel glioma therapeutics.
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