NcRNAs-mediated High Expression of TIMM8A Correlates with Poor Prognosis and Act As an Oncogene in Breast Cancer

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2022 May 3

PMID 35501914

Authors

Zhonglin Wang

Shuqin Li

Feng Xu

Jingyue Fu

Jie Sun

Xinli Gan

Chuang Yang

Zhongqi Mao

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is notorious for its increasing incidence for decades. Ascending evidence has demonstrated that translocase of inner mitochondrial membrane (TIMM) proteins play vital roles in progression of several types of human cancer. However, the biological behaviors and molecular mechanisms of TIMM8A in breast cancer remain not fully illustrated.

Methods: Pan-cancer analysis was firstly performed for TIMM8A's expression and prognosis by Oncomine database. Subsequently, TIMM8A-related noncoding RNAs (ncRNAs) were identified by a series of bioinformatics analyses and dual-luciferase reporter assay, including expression analysis, correlation analysis, and survival analysis. Moreover, the effect of TIMM8A on breast cancer proliferation and apoptosis was evaluated in vitro by CCK-8 assays, EdU cell proliferation assays, JC-1 mitochondrial membrane potential detection assays and Western blot assays and the in vivo effect was revealed through a patient-derived xenograft mouse model.

Results: We found that TIMM8A showed higher expression level in breast cancer and the higher TIMM8A mRNA expression group had a poorer prognosis than the lower TIMM8A group. hsa-circ-0107314/hsa-circ-0021867/hsa-circ-0122013 might be the three most potential upstream circRNAs of hsa-miR-34c-5p/hsa-miR-449a-TIMM8A axis in breast cancer. TIMM8A promotes proliferation of breast cancer cells in vitro and tumor growth in vivo.

Conclusion: Our results confirmed that ncRNAs-mediated upregulation of TIMM8A correlated with poor prognosis and act as an oncogene in breast cancer.

Citing Articles

Analysis of ROMO1 Expression Levels and Its Oncogenic Role in Gastrointestinal Tract Cancers.

Yaman S, Akidan O, Vatansever M, Misir S, Yaman S Curr Issues Mol Biol. 2024; 46(12):14394-14407.

PMID: 39727991 PMC: 11674390. DOI: 10.3390/cimb46120863.

Serum CD133-Associated Proteins Identified by Machine Learning Are Connected to Neural Development, Cancer Pathways, and 12-Month Survival in Glioblastoma.

Joyce T, Tasci E, Jagasia S, Shephard J, Chappidi S, Zhuge Y Cancers (Basel). 2024; 16(15).

PMID: 39123468 PMC: 11311306. DOI: 10.3390/cancers16152740.

Possible Role of miR-375-3p in Cervical Lymph Node Metastasis of Oral Squamous Cell Carcinoma.

Saika M, Nakashiro K, Tokuzen N, Shirai H, Uchida D Cancers (Basel). 2024; 16(8).

PMID: 38672573 PMC: 11049256. DOI: 10.3390/cancers16081492.

Organotypic 3D Cell-Architecture Impacts the Expression Pattern of miRNAs-mRNAs Network in Breast Cancer SKBR3 Cells.

Gastelum-Lopez M, Aguilar-Medina M, Garcia Mata C, Lopez-Gutierrez J, Romero-Quintana G, Bermudez M Noncoding RNA. 2023; 9(6).

PMID: 37987362 PMC: 10661268. DOI: 10.3390/ncrna9060066.

Combined signature of N7-methylguanosine regulators with their related genes and the tumor microenvironment: a prognostic and therapeutic biomarker for breast cancer.

Li T, Chen Z, Wang Z, Lu J, Chen D Front Immunol. 2023; 14:1260195.

PMID: 37868988 PMC: 10585266. DOI: 10.3389/fimmu.2023.1260195.

References

Wang Q, Wen Y, Li D, Xia J, Zhou C, Yan D . Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol. 2010; 29(1):77-83. DOI: 10.1007/s12032-010-9766-y. View

Bueno M, Ruiz-Sepulveda J, Quintela-Fandino M . Mitochondrial Inhibition: a Treatment Strategy in Cancer?. Curr Oncol Rep. 2021; 23(4):49. DOI: 10.1007/s11912-021-01033-x. View

DeSantis C, Ma J, Sauer A, Newman L, Jemal A . Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017; 67(6):439-448. DOI: 10.3322/caac.21412. View

Ning X, Sun L . Gene network analysis reveals a core set of genes involved in the immune response of Japanese flounder (Paralichthys olivaceus) against Vibrio anguillarum infection. Fish Shellfish Immunol. 2019; 98:800-809. DOI: 10.1016/j.fsi.2019.11.033. View

Vander Heiden M, Cantley L, Thompson C . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-33. PMC: 2849637. DOI: 10.1126/science.1160809. View

Huang Y, Zhou J, Luo S, Wang Y, He J, Luo P . Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44. Gut. 2016; 67(2):307-319. DOI: 10.1136/gutjnl-2016-311909. View

Tang W, Borgnia M, Hsu A, Esser L, Fox T, de Val N . Structures of AAA protein translocase Bcs1 suggest translocation mechanism of a folded protein. Nat Struct Mol Biol. 2020; 27(2):202-209. PMC: 8482623. DOI: 10.1038/s41594-020-0373-0. View

McBride H, Neuspiel M, Wasiak S . Mitochondria: more than just a powerhouse. Curr Biol. 2006; 16(14):R551-60. DOI: 10.1016/j.cub.2006.06.054. View

Neighbors A, Moss T, Holloway L, Yu S, Annese F, Skinner S . Functional analysis of a novel mutation in the TIMM8A gene that causes deafness-dystonia-optic neuronopathy syndrome. Mol Genet Genomic Med. 2020; 8(3):e1121. PMC: 7057109. DOI: 10.1002/mgg3.1121. View

10.

Jose C, Bellance N, Rossignol R . Choosing between glycolysis and oxidative phosphorylation: a tumor's dilemma?. Biochim Biophys Acta. 2010; 1807(6):552-61. DOI: 10.1016/j.bbabio.2010.10.012. View

11.

Li X, Deng S, Pang X, Song Y, Luo S, Jin L . LncRNA NEAT1 Silenced miR-133b Promotes Migration and Invasion of Breast Cancer Cells. Int J Mol Sci. 2019; 20(15). PMC: 6695844. DOI: 10.3390/ijms20153616. View

12.

Zhang X, Han S, Zhou H, Cai L, Li J, Liu N . TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non-small cell lung cancer patients. Mol Carcinog. 2019; 58(5):767-776. DOI: 10.1002/mc.22969. View

13.

Cai J, Chen J, Huang L, Wang C, Zhang W, Zhou Q . A Regulatory Network Contributing to Breast Cancer. Front Genet. 2021; 12:658154. PMC: 8375323. DOI: 10.3389/fgene.2021.658154. View

14.

Salhab M, Patani N, Jiang W, Mokbel K . High TIMM17A expression is associated with adverse pathological and clinical outcomes in human breast cancer. Breast Cancer. 2010; 19(2):153-60. DOI: 10.1007/s12282-010-0228-3. View

15.

Zong W, Rabinowitz J, White E . Mitochondria and Cancer. Mol Cell. 2016; 61(5):667-676. PMC: 4779192. DOI: 10.1016/j.molcel.2016.02.011. View

16.

Voabil P, de Bruijn M, Roelofsen L, Hendriks S, Brokamp S, van den Braber M . An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer. Nat Med. 2021; 27(7):1250-1261. DOI: 10.1038/s41591-021-01398-3. View

17.

Pelicano H, Zhang W, Liu J, Hammoudi N, Dai J, Xu R . Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Res. 2014; 16(5):434. PMC: 4303115. DOI: 10.1186/s13058-014-0434-6. View

18.

Zhang X, Lewis M . Establishment of Patient-Derived Xenograft (PDX) Models of Human Breast Cancer. Curr Protoc Mouse Biol. 2015; 3(1):21-9. DOI: 10.1002/9780470942390.mo120140. View

19.

Nagley P, Higgins G, Atkin J, Beart P . Multifaceted deaths orchestrated by mitochondria in neurones. Biochim Biophys Acta. 2009; 1802(1):167-85. DOI: 10.1016/j.bbadis.2009.09.004. View

20.

Bonora E, Evangelisti C, Bonichon F, Tallini G, Romeo G . Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas. Br J Cancer. 2006; 95(11):1529-36. PMC: 2360750. DOI: 10.1038/sj.bjc.6603455. View