Mitochondrial glycerophosphate dehydrogenase (MGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin in the liver. There are no data on the expression and role of MGPDH as a metformin target in cancer. In this study, we evaluated MGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism. We analyzed MGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy. The effects of metformin on MGPDH expression were determined by qRT-PCR and Western blot analysis. Seahorse analyzer was utilized to assess the effects of metformin on OXPHOS and glycolysis in thyroid cancer cells. We analyzed the effects of metformin on tumor growth and MGPDH expression in metastatic thyroid cancer mouse models. We show for the first time that MGPDH is overexpressed in thyroid cancer compared with normal thyroid. We demonstrate that MGPDH regulates human thyroid cancer cell growth and OXPHOS rate Metformin treatment is associated with downregulation of MGPDH expression and inhibition of OXPHOS in thyroid cancer Cells characterized by high MGPDH expression are more sensitive to OXPHOS-inhibitory effects of metformin and growth-inhibitory effects of metformin and Our study established MGPDH as a novel regulator of thyroid cancer growth and metabolism that can be effectively targeted by metformin. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3167 | DOI Listing |
J Endocrinol Invest
January 2025
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Purpose: Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the tumorigenesis and progression of various cancers. However, the functional roles of lncRNAs in papillary thyroid cancer (PTC) remain unclear. In this study, we investigated the functional role of the lncRNA FAM111A-DT in PTC progression and the underlying mechanisms.
View Article and Find Full Text PDFKaohsiung J Med Sci
January 2025
Department of Neck Surgery, Sanming First Hospital Affiliated to Fujian Medical University, Sanming, China.
Metastasis is the trigger of death in anaplastic thyroid cancer (ATC) patients, yet the specific mechanisms at play are still largely enigmatic. While the involvement of LARP1 in the metastatic process of various cancers has been documented, there is a noticeable gap in the literature regarding its potential influence on ATC metastasis. Molecular studies probed LARP1 expression within ATC cells, with subsequent in vitro experiments examining the effects of LARP1 on ATC cell metastasis and the mTOR signaling cascade.
View Article and Find Full Text PDFFood Nutr Res
December 2024
School of Public Health, Chengdu Medical College, Chengdu, China.
Background: Breast cancer is a leading cause of cancer-related mortality among women globally, with triple-negative breast cancer (TNBC) being particularly aggressive. Delphinidin (Dp), an anthocyanin monomer, has shown promising health benefits.
Objective: This study investigates the effects of Dp on TNBC and aims to elucidate its specific mechanisms of action.
Korean J Radiol
January 2025
Department of Radiology, Prof. Dr. Cemil Tascioglu City Hospital, University of Health Sciences, Istanbul, Türkiye.
Korean J Radiol
January 2025
Department of Radiology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea.
Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.
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