Tumor Biology

, Volume 37, Issue 7, pp 9789–9796 | Cite as

GRIM-19 inhibition induced autophagy through activation of ERK and HIF-1α not STAT3 in Hela cells

  • Xin Yue
  • Peiwei Zhao
  • Kongming Wu
  • Juan Huang
  • Wen Zhang
  • Yaogui Wu
  • Xiaohui Liang
  • Xuelian He
Original Article

Abstract

Gene associated with retinoid-interferon-induced mortality (GRIM-19), an important subunit of mitochondrial complex I, has been identified as a tumor suppressor, and its reduced expression has been reported to be associated with tumorigenesis and metastasis. Autophagy has been proposed as a protective mechanism for cell survival under various stresses, including chemotherapy. However, it remains unknown whether GRIM-19 is linked to autophagy and chemotherapy resistance. Here, we showed that suppression of GRIM-19 by shRNA enhanced cell-type-dependent autophagy by activating extracellular regulated protein kinase (ERK) and hypoxia inducible factor-1a (HIF-1a) in a reactive oxygen species (ROS)-mediated manner, and thereby conferred resistance to paclitaxel. Besides, the antioxidant N-acetyl-l-cysteine (NAC) and autophagy inhibitor 3-MA could in part overcome this resistance. We also found that GRIM-19 expression was significantly correlated with clinical stage and grade in patients with cervical cancers. Taken together, our results indicated that GRIM-19 inhibition induced autophagy and chemotherapy resistance, which could affect prognosis of cervical cancers. Our study has identified new function of GRIM-19 and its underlying mechanism, and it will provide possible avenues for therapeutic targeting in cervical cancers.

Keywords

GRIM-19 Autophagy Cervical cancer Chemotherapy ERK HIF-1a 

Notes

Acknowledgments

This study was funded by Wuhan Yellow Crane Medical Talent Program Grant No. 2015-12 and by the supporting program of the Ministry of Human Resource of China Oversea Returned scholars, and the National Natural Science Foundation of China (Grant No. 81572608).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Xin Yue
    • 1
  • Peiwei Zhao
    • 1
  • Kongming Wu
    • 2
  • Juan Huang
    • 3
  • Wen Zhang
    • 3
  • Yaogui Wu
    • 4
  • Xiaohui Liang
    • 5
  • Xuelian He
    • 1
  1. 1.Clinical Research Center, Wuhan Medical and Healthcare Center for Women and ChildrenWuhanChina
  2. 2.Department of Oncology, Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  3. 3.Department of PathologyWuhan Medical and Healthcare Center for Women and ChildrenWuhanChina
  4. 4.School of Public HealthWuhan UniversityWuhanChina
  5. 5.Department of Oncology, Renmin HospitalWuhan UniversityWuhanChina

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