Research Paper|Volume 12, Issue 17|pp 16963—16980

PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion

LiLi Chen^1,², XiaoDan Mao¹, MeiMei Huang³, HuiFang Lei¹, LiFang Xue³, PengMing Sun^1,^3,⁴

¹Laboratory of Gynecological Oncology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. of China
²Reproductive Center, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. of China
³Department of Gynecology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. of China
⁴Fujian Key Laboratory of Women and Children's Critical Diseases Research, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, Fujian, P.R. of China

Received: January 14, 2020Accepted: June 1, 2020Published: September 13, 2020

Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored.

Results: Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer. Silencing of PGC-1α reduced ERRα activation and inhibited epithelial-mesenchymal-transition phenotypes, resulting in significant inhibition of invasion and migration. Overexpression of ERRα led to enhanced PGC-1α expression and increased activity of TFEB, promoting epithelial-mesenchymal-transition in endometrial cancer cells.

Conclusions: PGC-1α and ERRα induce the epithelial-mesenchymal-transition therefore invasion and migration in endometrial cancer, and may be novel biomarkers to predict the risk of advanced myometrial invasion.

Methods: PGC-1α, ERRα, and vimentin expression was analyzed in tissue microarrays using immunohistochemistry. PGC-1α and ERRα expression in endometrial cancer cell lines was investigated using quantitative PCR and western blotting analyses after infection with lentivirus-mediated small interfering RNA (siRNA) targeting PGC-1α (siRNA-PGC-1α) or overexpressing ERRα. E-cadherin and vimentin levels were determined using western blotting and cell immunouorescence analyses. Cell migration and invasiveness were evaluated using scratch and trans-well chamber assays.