High Expression of TRIM24 Predicts Worse Prognosis and Promotes Proliferation and Metastasis of Epithelial Ovarian Cancer

Overview

Journal J Ovarian Res

Publisher Biomed Central

Specialties Gynecology & Obstetrics
Reproductive Medicine

Date 2022 Feb 2

PMID 35105347

Authors

Liwei Zhang

Hong Chen

Baijuan Ding

Wei Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC.

Results: Data from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan-Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman's correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT.

Conclusion: Our results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.

Citing Articles

The tripartite motif-containing 24 is a multifunctional player in human cancer.

Yao Y, Zhou S, Yan Y, Fu K, Xiao S Cell Biosci. 2024; 14(1):103.

PMID: 39160596 PMC: 11334367. DOI: 10.1186/s13578-024-01289-3.

USP7 inhibits the progression of nasopharyngeal carcinoma via promoting SPLUNC1-mediated M1 macrophage polarization through TRIM24.

Liu H, Tang L, Gong S, Xiao T, Yang H, Gu W Cell Death Dis. 2023; 14(12):852.

PMID: 38129408 PMC: 10739934. DOI: 10.1038/s41419-023-06368-w.

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.

Talukdar P, Chatterji U Signal Transduct Target Ther. 2023; 8(1):427.

PMID: 37953273 PMC: 10641101. DOI: 10.1038/s41392-023-01651-w.

Readout of histone methylation by Trim24 locally restricts chromatin opening by p53.

Isbel L, Iskar M, Durdu S, Weiss J, Grand R, Hietter-Pfeiffer E Nat Struct Mol Biol. 2023; 30(7):948-957.

PMID: 37386214 PMC: 10352137. DOI: 10.1038/s41594-023-01021-8.

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities.

Liu X, Wang A, Shi Y, Dai M, Liu M, Cai H Molecules. 2023; 28(3).

PMID: 36770884 PMC: 9919707. DOI: 10.3390/molecules28031217.

References

Tsai W, Wang Z, Yiu T, Akdemir K, Xia W, Winter S . TRIM24 links a non-canonical histone signature to breast cancer. Nature. 2010; 468(7326):927-32. PMC: 3058826. DOI: 10.1038/nature09542. View

Pathiraja T, Thakkar K, Jiang S, Stratton S, Liu Z, Gagea M . TRIM24 links glucose metabolism with transformation of human mammary epithelial cells. Oncogene. 2014; 34(22):2836-45. PMC: 4370790. DOI: 10.1038/onc.2014.220. View

Jayson G, Kohn E, Kitchener H, Ledermann J . Ovarian cancer. Lancet. 2014; 384(9951):1376-88. DOI: 10.1016/S0140-6736(13)62146-7. View

Miao Z, Wang Z, Zhao T, Xu Y, Wu J, Liu X . TRIM24 is upregulated in human gastric cancer and promotes gastric cancer cell growth and chemoresistance. Virchows Arch. 2015; 466(5):525-32. DOI: 10.1007/s00428-015-1737-4. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Zhang L, Yin Y, Chen H, Feng S, Liu J, Chen L . TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression. Neuro Oncol. 2020; 22(12):1797-1808. PMC: 7746937. DOI: 10.1093/neuonc/noaa138. View

Jiang S, Minter L, Stratton S, Yang P, Abbas H, Akdemir Z . TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice. J Hepatol. 2014; 62(2):371-9. PMC: 4772153. DOI: 10.1016/j.jhep.2014.09.026. View

Fang Z, Deng J, Zhang L, Xiang X, Yu F, Chen J . TRIM24 promotes the aggression of gastric cancer via the Wnt/β-catenin signaling pathway. Oncol Lett. 2017; 13(3):1797-1806. PMC: 5403329. DOI: 10.3892/ol.2017.5604. View

Zhang L, Yin A, Cheng J, Huang H, Li X, Zhang Y . TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway. Oncogene. 2014; 34(5):600-10. DOI: 10.1038/onc.2013.593. View

10.

Li H, Sun L, Tang Z, Fu L, Xu Y, Li Z . Overexpression of TRIM24 correlates with tumor progression in non-small cell lung cancer. PLoS One. 2012; 7(5):e37657. PMC: 3364288. DOI: 10.1371/journal.pone.0037657. View

11.

Lheureux S, Braunstein M, Oza A . Epithelial ovarian cancer: Evolution of management in the era of precision medicine. CA Cancer J Clin. 2019; 69(4):280-304. DOI: 10.3322/caac.21559. View

12.

Yu Y, Cai L, Wang X, Cheng S, Zhang D, Jian W . BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma. Cancer Sci. 2020; 111(5):1555-1566. PMC: 7226287. DOI: 10.1111/cas.14376. View

13.

Groner A, Cato L, de Tribolet-Hardy J, Bernasocchi T, Janouskova H, Melchers D . TRIM24 Is an Oncogenic Transcriptional Activator in Prostate Cancer. Cancer Cell. 2016; 29(6):846-858. PMC: 5124371. DOI: 10.1016/j.ccell.2016.04.012. View

14.

Lin L, Zhao W, Sun B, Wang X, Liu Q . Overexpression of TRIM24 is correlated with the progression of human cervical cancer. Am J Transl Res. 2017; 9(2):620-628. PMC: 5340696. View

15.

Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L . The tripartite motif family identifies cell compartments. EMBO J. 2001; 20(9):2140-51. PMC: 125245. DOI: 10.1093/emboj/20.9.2140. View

16.

Jain A, Allton K, Duncan A, Barton M . TRIM24 is a p53-induced E3-ubiquitin ligase that undergoes ATM-mediated phosphorylation and autodegradation during DNA damage. Mol Cell Biol. 2014; 34(14):2695-709. PMC: 4097665. DOI: 10.1128/MCB.01705-12. View

17.

Meroni G, Diez-Roux G . TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases. Bioessays. 2005; 27(11):1147-57. DOI: 10.1002/bies.20304. View

18.

Le Douarin B, Nielsen A, Garnier J, Ichinose H, Jeanmougin F, Losson R . A possible involvement of TIF1 alpha and TIF1 beta in the epigenetic control of transcription by nuclear receptors. EMBO J. 1996; 15(23):6701-15. PMC: 452494. View

19.

Cui Z, Cao W, Li J, Song X, Mao L, Chen W . TRIM24 overexpression is common in locally advanced head and neck squamous cell carcinoma and correlates with aggressive malignant phenotypes. PLoS One. 2013; 8(5):e63887. PMC: 3661592. DOI: 10.1371/journal.pone.0063887. View

20.

Liu X, Huang Y, Yang D, Li X, Liang J, Lin L . Overexpression of TRIM24 is associated with the onset and progress of human hepatocellular carcinoma. PLoS One. 2014; 9(1):e85462. PMC: 3883694. DOI: 10.1371/journal.pone.0085462. View