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Updated: Feb 22, 2026
Hypoxia Alters miRNAs Levels Involved in Non-Mendelian Inheritance of Autism Spectrum Disorder in Mice
Published on: July 11, 2025
MicroRNA-320 regulates autophagy in retinoblastoma by targeting hypoxia inducible factor-1α
Yong Liang1, Xi Chen1, Zhu Liang1
1Department of Ophthalmology, The Ninth People's Hospital of Chongqing, Chongqing 400700, P.R. China.
Abstract:
Retinoblastoma (RB) is the most common malignancy in children. Due to refractory mechanisms of chemoresistance and the toxicity of chemotherapies, novel therapies for RB treatment are urgently required. MicroRNA-320 (miR-320) is believed to be associated with the tumorigenesis of RB, although the mechanism remains unclear. Considering the hypoxic intratumoral region, the roles of miR-320 and hypoxia inducible factor-1α (HIF-1α) in the regulation of autophagy were investigated in 30 human RB samples and WERI-RB1 cells. The results demonstrated that HIF-1α was the downstream target of miR-320, and decreased miRNA-320 or HIF-1α lead to the inhibition of autophagy in WERI-RB1 cells. Compared with WERI-RB1 cells that were not transfected, silenced HIF-1α caused a 1.41-fold increase (P<0.01) in p62, a 2.71-fold decrease of Beclin1, and inhibited miRNA-320. Silenced HIF-1α also resulted in 7.29- and 7.43-fold increases in phosphorylated-mechanistic target of rapamycin (mTOR) and mTOR, respectively. In conclusion, the present results suggest that miRNA-320 may regulate the development of autophagy by targeting HIF-1α and autophagy-related proteins in RB under hypoxic conditions.
Insights
MicroRNA-320 targets hypoxia-inducible factor-1α (HIF-1α) to regulate autophagy in retinoblastoma (RB) cells. This finding offers potential new therapeutic strategies for treating this childhood cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Biology
Background:
- Retinoblastoma (RB) is the most frequent childhood cancer.
- Current chemotherapy for RB faces challenges due to chemoresistance and toxicity.
- Novel therapeutic approaches are needed for effective RB treatment.
Purpose of the Study:
- To investigate the roles of microRNA-320 (miR-320) and hypoxia-inducible factor-1α (HIF-1α) in regulating autophagy in retinoblastoma.
- To elucidate the mechanism linking miR-320, HIF-1α, and autophagy in RB, particularly under hypoxic conditions.
Main Methods:
- Analysis of 30 human retinoblastoma samples and WERI-RB1 cells.
- Investigation of miR-320 and HIF-1α interactions.
- Assessment of autophagy-related proteins, including p62, Beclin1, and mTOR signaling pathways.
Main Results:
- Hypoxia-inducible factor-1α (HIF-1α) was identified as a downstream target of microRNA-320 (miR-320).
- Reduced miR-320 or HIF-1α levels led to the inhibition of autophagy in WERI-RB1 cells.
- Silencing HIF-1α increased p62 and phosphorylated-mTOR/mTOR, while decreasing Beclin1 and inhibiting miR-320.
Conclusions:
- MicroRNA-320 (miR-320) appears to regulate autophagy development in retinoblastoma (RB) by targeting HIF-1α and autophagy-related proteins.
- These findings suggest a potential therapeutic pathway involving miR-320 and HIF-1α for RB treatment under hypoxic conditions.
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