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.

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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