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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
Published on: October 28, 2019
Modulation of autophagy in exJSRV-env-transfected cells through the Akt/mTOR and MAPK signaling pathway
Xiaolin Sun1, Fangyuan Du1, Shuying Liu1
1College of Veterinary Medicine, Inner Mongolia Agricultural University, Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture, Hohhot 010018, China.
Abstract:
The envelope (Env) of Jaagsiekte sheep retrovirus (JSRV) is an oncoprotein of ovine pulmonary adenocarcinoma (OPA). Autophagy is involved in different cancers, but how it is carcinogenic in JSRV Env is unclear. Modulation of autophagy in exJSRV-env-NM-transfected cells through the Akt/mTOR and MAPK signaling pathway was studied, and we observed strong positive labeling of p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-p38 and p-JNK in tumor cells and typical type II pneumocytes in naturally infected OPA lung tissues, which was co-aligned with JSRV-Env positive cells as shown by immunohistochemical and microscopic analysis. Akt/mTOR and MAPK pathways were activated in OPA lung and JSRV-Env transfected NIH 3T3 cells. Decreased Beclin1 and LC3 II/I suggested that autophagy was inhibited in OPA lung and JSRV-Env transfected NIH 3T3 cells. Beclin1 and LC3 II/I increased in JSRV-Env transfected NIH3T3 cells treated with mTOR inhibitor (rapamycin), ERK1/2 inhibitor (PD 98059), p38 inhibitor (SB 203580) and JNK inhibitor (SP 600125), suggesting that Akt/mTOR and MAPK pathways were responsible for JSRV-Env decreased autophagy. In conclusion, JSRV Env decreased autophagy in JSRV-Env transfected NIH3T3 cells through Akt/mTOR and MAPK pathways, in particular, JNK and p38 pathways.
Insights
Jaagsiekte sheep retrovirus envelope (Env) oncoprotein inhibits autophagy via Akt/mTOR and MAPK pathways. This study clarifies JSRV Env
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Jaagsiekte sheep retrovirus (JSRV) envelope (Env) is an oncoprotein implicated in ovine pulmonary adenocarcinoma (OPA).
- The role of autophagy in JSRV Env-induced carcinogenesis is not fully understood.
- Autophagy modulation is a potential target in cancer therapy.
Purpose of the Study:
- To investigate the modulation of autophagy in JSRV Env-transfected cells.
- To elucidate the involvement of Akt/mTOR and MAPK signaling pathways in JSRV Env-mediated autophagy.
- To determine the mechanism by which JSRV Env affects autophagy.
Main Methods:
- Immunohistochemical and microscopic analysis of OPA lung tissues and JSRV Env-transfected NIH 3T3 cells.
- Assessment of autophagy markers (Beclin1, LC3 II/I) and signaling pathway proteins (p-Akt, p-mTOR, p-MEK1/2, p-ERK1/2, p-38, p-JNK).
- Treatment of transfected cells with specific inhibitors for mTOR, ERK1/2, p38, and JNK pathways.
Main Results:
- Activated Akt/mTOR and MAPK pathways were observed in OPA lung tissues and JSRV Env-transfected cells.
- Autophagy was inhibited in OPA lung tissues and JSRV Env-transfected cells, indicated by decreased Beclin1 and LC3 II/I.
- Inhibition of autophagy markers was reversed by treatment with mTOR, ERK1/2, p38, and JNK inhibitors.
Conclusions:
- JSRV Env decreases autophagy in transfected cells through the activation of Akt/mTOR and MAPK signaling pathways.
- The JNK and p38 pathways are particularly implicated in JSRV Env-mediated autophagy inhibition.
- Understanding this mechanism provides insights into JSRV-induced OPA pathogenesis.
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