Protein Arginine Methyltransferases 5 (PRMT5) affect Multiple Stages of Autophagy and Modulate Autophagy-related
Jing Kong1, Zhe Wang1, Yong Zhang2
1Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, P.R. China.
Background:
Autophagy disorders are linked to human cancer, and the details of their mechanisms remain unclear.
Objective:
To investigate the regulatory role of PRMT5 in the autophagy of breast cancer cells.
Methods:
Human breast adenocarcinoma cell lines (MDA-MB-231, MCF7) were cultured. Plasmids of overexpression and down-regulation of PRMT5 were transfected into MDA-MB-231 and MCF7 cells. The MTT assay was used to determine the proliferation of MDA-MB-231 and MCF7 cells. A western blotting assay was used to verify the expression of autophagy-associated molecules. Immunofluorescence was applied to observe the expression of GFP-LC3.
Results:
The expression of PRMT5 decreased the sensitivity to rapamycin and nutrient deprivation. PRMT5 acts as an oncogene to promote cell proliferation and influences migration and stamness. PRMT5 expression elevated the autophagic activity initiated by EBSS and Rapamycin. PRMT5 was necessary and sufficient to enhance stress-induced autophagy. PRMT5 could improve several autophagy- related gene expressions. Atg5 expression could be regulated by activating the PRMT5 and PDCD4 molecules. The PRMT5 molecule could mediate the regulation of ULK1 expression.
Conclusion:
PRMT5 influenced multiple stages of autophagy in controlling autophagy and tumorigenesis. Autophagy-related PRMT5 might be a respected target for therapeutic interventions in cancers. This study would provide new ideas for treating and selecting breast cancer targets.
Insights
Protein arginine methyltransferase 5 (PRMT5) promotes breast cancer cell proliferation and enhances autophagy. Targeting PRMT5 may offer new therapeutic strategies for breast cancer treatment.
Area of Science:
- Cellular Biology
- Oncology
- Molecular Mechanisms
Background:
- Autophagy disorders are implicated in human cancers, but their precise mechanisms are not fully understood.
- Investigating the role of specific molecules in cancer-related autophagy is crucial for therapeutic development.
Purpose of the Study:
- To elucidate the regulatory function of Protein Arginine Methyltransferase 5 (PRMT5) in the autophagy process within breast cancer cells.
- To determine if PRMT5 influences breast cancer cell proliferation and autophagy.
Main Methods:
- Utilized human breast adenocarcinoma cell lines (MDA-MB-231, MCF7).
- Manipulated PRMT5 expression via overexpression and down-regulation plasmids.
- Assessed cell proliferation using MTT assays.
- Analyzed autophagy-associated molecule expression via Western blotting and immunofluorescence (GFP-LC3).
Main Results:
- PRMT5 expression decreased sensitivity to rapamycin and nutrient deprivation.
- PRMT5 acts as an oncogene, promoting cell proliferation, migration, and stemness.
- Elevated PRMT5 expression enhanced autophagic activity induced by EBSS and rapamycin.
- PRMT5 was essential for enhancing stress-induced autophagy and regulating autophagy-related gene expression (e.g., Atg5, ULK1).
Conclusions:
- PRMT5 plays a significant role in regulating autophagy at multiple stages, impacting tumorigenesis.
- Autophagy-related PRMT5 presents a potential therapeutic target for cancer interventions.
- This research offers novel insights for breast cancer treatment and target selection.
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