MiR-134-3p Driven by Anisomycin Impairs Ovarian Cancer Stem Cell Activity Through Inhibiting GPR137 Expression

Overview

Journal J Cancer

Specialty Oncology

Date 2023 Nov 29

PMID 38021163

Authors

Lele Ling

Yichao Wen

Haiyang Chen

Ying Xiong

Xin Liu

Juan Chen

Te Liu

Bimeng Zhang

Affiliations

Soon will be listed here.

Abstract

: Ovarian cancer recurrence and metastasis are predominantly attributed to ovarian cancer stem cells; however, the mechanism by which anisomycin regulates human ovarian cancer stem cells (HuOCSCs) remains unclear. : cDNA microArray was used to screen microRNAs (miRNAs) targeted by anisomycin, and RT-qPCR validated the miRNA targets. TargetScan database, GO enrichment analysis, and RT-qPCR, accompanied by a fluorescent reporter system, were employed to verify the miRNA target genes. experimental cell proliferation inhibition assay, flow cytometry, Transwell, angiogenesis assay, and transplantation tumor assay were implemented to assess the ability of the overexpressed miRNAs to hinder HuOCSC activity. Western blot, RT-qPCR, and immunofluorescence were applied to measure the transcriptional and protein-level expression of the miRNA target genes and their related genes. Bioinformatic analysis predicted and deciphered the role of the miRNA target genes and related genes in the development and prognosis of ovarian cancer. The expression levels of multiple DLK1-DIO3 imprinted microRNA cluster members were altered by anisomycin, among which miR-134-3p expression was most significantly elevated. miR-134-3p overexpression significantly suppressed HuOCSC activity. The screening and validation of target genes uncovered that miR-134-3p was able to markedly suppress GPR137 expression. Additionally, miR-134-3p regulated the cytoskeleton, migration-related protein in the NDEL1/DYNEIN/TUBA1A axis through targeting GPR137. Bioinformatics prediction unveiled a close association of GPR137, NDEL1, DYNC1H1, and TUBA1A with ovarian cancer development and prognosis. The activity of HuOCSCs may be compromised by anisomycin through the regulation of miR-134-3p, which inhibits the GPR137/NDEL1/DYNEIN/TUBA1A axis.

Citing Articles

GPR137-RAB8A activation promotes ovarian cancer development via the Hedgehog pathway.

Tang C, Li L, Zhu C, Xu Q, An Z, Xu S J Exp Clin Cancer Res. 2025; 44(1):22.

PMID: 39856733 PMC: 11761205. DOI: 10.1186/s13046-025-03275-0.

References

Benetatos L, Vartholomatos G, Hatzimichael E . DLK1-DIO3 imprinted cluster in induced pluripotency: landscape in the mist. Cell Mol Life Sci. 2014; 71(22):4421-30. PMC: 11113449. DOI: 10.1007/s00018-014-1698-9. View

Seo B, Min K, Kim S, Park J, Park W, Lee T . Anisomycin treatment enhances TRAIL-mediated apoptosis in renal carcinoma cells through the down-regulation of Bcl-2, c-FLIP(L) and Mcl-1. Biochimie. 2012; 95(4):858-65. DOI: 10.1016/j.biochi.2012.12.002. View

Chen W, Yang W, Zhang C, Liu T, Zhu J, Wang H . Modulation of the p38 MAPK Pathway by Anisomycin Promotes Ferroptosis of Hepatocellular Carcinoma through Phosphorylation of H3S10. Oxid Med Cell Longev. 2022; 2022:6986445. PMC: 9715334. DOI: 10.1155/2022/6986445. View

Gao L, Xue B, Xiang B, Liu K . Arsenic trioxide disturbs the LIS1/NDEL1/dynein microtubule dynamic complex by disrupting the CLIP170 zinc finger in head and neck cancer. Toxicol Appl Pharmacol. 2020; 403:115158. PMC: 8080511. DOI: 10.1016/j.taap.2020.115158. View

Gao Y, Zeng S, Xu X, Li H, Yao S, Song K . Deep learning-enabled pelvic ultrasound images for accurate diagnosis of ovarian cancer in China: a retrospective, multicentre, diagnostic study. Lancet Digit Health. 2022; 4(3):e179-e187. DOI: 10.1016/S2589-7500(21)00278-8. View

Szklarczyk D, Gable A, Nastou K, Lyon D, Kirsch R, Pyysalo S . The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2020; 49(D1):D605-D612. PMC: 7779004. DOI: 10.1093/nar/gkaa1074. View

Cheng W, Liu T, Wan X, Gao Y, Wang H . MicroRNA-199a targets CD44 to suppress the tumorigenicity and multidrug resistance of ovarian cancer-initiating cells. FEBS J. 2012; 279(11):2047-59. DOI: 10.1111/j.1742-4658.2012.08589.x. View

Thomas P, Campbell M, Kejariwal A, Mi H, Karlak B, Daverman R . PANTHER: a library of protein families and subfamilies indexed by function. Genome Res. 2003; 13(9):2129-41. PMC: 403709. DOI: 10.1101/gr.772403. View

Jiang Y, Song Y, Wang R, Hu T, Zhang D, Wang Z . NFAT1-Mediated Regulation of NDEL1 Promotes Growth and Invasion of Glioma Stem-like Cells. Cancer Res. 2019; 79(10):2593-2603. DOI: 10.1158/0008-5472.CAN-18-3297. View

10.

Honda S, Chatterjee A, Leichter A, Miyagi H, Minato M, Fujiyoshi S . A MicroRNA Cluster in the Imprinted Region on Chromosome 14q32.2 Is Dysregulated in Metastatic Hepatoblastomas. Front Oncol. 2020; 10:513601. PMC: 7689214. DOI: 10.3389/fonc.2020.513601. View

11.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

12.

Murali R, Balasubramaniam V, Srinivas S, Sundaram S, Venkatraman G, Warrier S . Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence. Metabolites. 2023; 13(4). PMC: 10141515. DOI: 10.3390/metabo13040560. View

13.

Chang C, Liu T, Huang Y, Qin W, Yang H, Chen J . MicroRNA-134-3p is a novel potential inhibitor of human ovarian cancer stem cells by targeting RAB27A. Gene. 2017; 605:99-107. DOI: 10.1016/j.gene.2016.12.030. View

14.

Lheureux S, Gourley C, Vergote I, Oza A . Epithelial ovarian cancer. Lancet. 2019; 393(10177):1240-1253. DOI: 10.1016/S0140-6736(18)32552-2. View

15.

Wang Y, Liu T, Pan W, Chi H, Chen J, Yu Z . Small molecule compounds alleviate anisomycin-induced oxidative stress injury in SH-SY5Y cells via downregulation of p66shc and Aβ1-42 expression. Exp Ther Med. 2016; 11(2):593-600. PMC: 4734097. DOI: 10.3892/etm.2015.2921. View

16.

Yu C, Xing F, Tang Z, Bronner C, Lu X, Di J . Anisomycin suppresses Jurkat T cell growth by the cell cycle-regulating proteins. Pharmacol Rep. 2013; 65(2):435-44. DOI: 10.1016/s1734-1140(13)71019-3. View

17.

Tang Z, Xing F, Chen D, Yu Y, Yu C, Di J . In vivo toxicological evaluation of Anisomycin. Toxicol Lett. 2011; 208(1):1-11. DOI: 10.1016/j.toxlet.2011.10.001. View

18.

Zhang S, Balch C, Chan M, Lai H, Matei D, Schilder J . Identification and characterization of ovarian cancer-initiating cells from primary human tumors. Cancer Res. 2008; 68(11):4311-20. PMC: 2553722. DOI: 10.1158/0008-5472.CAN-08-0364. View

19.

Luk J, Burchard J, Zhang C, Liu A, Wong K, Shek F . DLK1-DIO3 genomic imprinted microRNA cluster at 14q32.2 defines a stemlike subtype of hepatocellular carcinoma associated with poor survival. J Biol Chem. 2011; 286(35):30706-30713. PMC: 3162431. DOI: 10.1074/jbc.M111.229831. View

20.

Gao Y, Liu T, Huang Y . MicroRNA-134 suppresses endometrial cancer stem cells by targeting POGLUT1 and Notch pathway proteins. FEBS Lett. 2014; 589(2):207-14. DOI: 10.1016/j.febslet.2014.12.002. View