1. Academic Validation
  2. ACSM3 suppresses the pathogenesis of high-grade serous ovarian carcinoma via promoting AMPK activity

ACSM3 suppresses the pathogenesis of high-grade serous ovarian carcinoma via promoting AMPK activity

  • Cell Oncol (Dordr). 2022 Feb;45(1):151-161. doi: 10.1007/s13402-021-00658-1.
Xu Yang  # 1 GuiXia Wu  # 2 Qin Zhang 3 Xia Chen 3 Juan Li 3 Qian Han 3 Lei Yang 3 Chendi Wang 3 Mei Huang 3 Yun Li 3 Jiao Chen 3 LiLi 3 Haiying Wang 3 Kaijiang Liu 4
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, The Fifth Affiliated People's Hospital of Chengdu University of Traditional Chinese Medicine, No. 33, Mashi Street, Wenjiang District, Chengdu, 610000, Sichuan, People's Republic of China. zhizihuakai@cdutcm.edu.cn.
  • 2 Department of Physiology, School of Basic Medicine, Xinjiang Medical University, Urumchi, Xinjiang Uygur Autonomous Region, People's Republic of China.
  • 3 Department of Obstetrics and Gynecology, The Fifth Affiliated People's Hospital of Chengdu University of Traditional Chinese Medicine, No. 33, Mashi Street, Wenjiang District, Chengdu, 610000, Sichuan, People's Republic of China.
  • 4 Department of Gynecological Oncology, Ren Ji Hospital, School of Medicine, Shanghai JiaoTong University, No145 Middle Shandong Road, Huangpu District, Shanghai, 200001, People's Republic of China. liukaijiang@263.net.
  • # Contributed equally.
Abstract

Purpose: Ovarian carcinoma is the fifth commonest malignancy in females and exhibits a high recurrence rate. High-grade serous ovarian carcinoma (HGSOC) is the main histologic subtype. It displays extensive genetic heterogeneity. Here, we aimed to identify potential therapeutic targets for HGSOC.

Methods: Both bioinformatic data from TCGA and 73 pairs of tumor and normal samples from patients were analyzed to reveal the expression level of ACSM3 in HGSOC. Next, cellular and animal experiments, including cell proliferation, colony formation and xenograft assays were performed to explore the suppressive function of ACSM3. Finally, biochemical methods, AMP/ATP ratio measurements and Western blotting were used to elucidate the mechanism underlying the ACSM3-AMPK axis in HGSOC.

Results: After analyzing transcriptome data of TCGA HGSOC samples, we found that ACSM3 is down-regulated in patient samples compared with normal controls. This observation was validated using data from primary clinical samples. Proliferation, soft agar colony formation and xenograft assays revealed that ACSM3 is able to suppress HGSOC tumor growth both in vitro and in vivo. Moreover, we found that ACSM3 overexpression increased the AMP/ATP ratio and the phosphorylation level of AMPK at threonine 172. In addition, we found that AMPK silencing in EFO21 and SKOV3 cells completely abolished the anti-oncogenic effect of ACSM3.

Conclusion: Our data indicate that the ACSM3-AMPK axis is involved in the pathogenesis of HGSOC and, as such, may act as a therapeutic target for this Cancer.

Keywords

ACSM3; AMPK; HGSOC; Ovarian carcinoma.

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