LncRNA DNM1P35 Sponges Hsa-mir-326 to Promote Ovarian Cancer Progression

Overview

Journal Sci Rep

Specialty Science

Date 2024 Dec 29

PMID 39732940

Authors

Mei Shen

Yun Mao

Xiaoshi Wang

Jinsong Huang

Qingsong Zhang

Jinwei Zhang

Affiliations

Soon will be listed here.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in cancer progression. We found lncRNA DNM1P35 is elevated in ovarian tumors compared to normal tissues, and demonstrated that lncRNA DNM1P35 promoted cancer cell proliferation, migration and invasion in SK-OV-3 and OVCAR-3 cell lines. Furthermore, lncRNA DNM1P35 also facilitated the epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Mechanistic studies identified microRNA-326 (miR-326) as a target of lncRNA DNM1P35. Overexpression of miR-326 diminished the tumor-promoting activity of lncRNA DNM1P35, resulting in reduction of Zinc finger E-box-binding homeobox 1 (ZEB1) expression and EMT features. We further revealed that ZEB1, a master transcription factor for EMT that is negatively regulated by miR-326, was essential for lncRNA DNM1P35-mediated cancer cell progression and EMT. Loss of ZEB1 led to compromised pro-tumoral activity of lncRNA DNM1P35. In vivo studies using a xenograft mouse model of ovarian cancer revealed that tumors with higher levels of lncRNA DNM1P35 led to shorter survival, increased tumor burden, as well as elevated expression of proliferative marker Ki67 and EMT marker ZEB1. Our comprehensive study underscored the significance of lncRNA DNM1P35 in ovarian cancer progression, elucidating the underlying mechanism through miR-326/ZEB1 axis to promote ovarian cancer progression.

References

Pronina I, Uroshlev L, Moskovtsev A, Zaichenko D, Filippova E, Fridman M . Dysregulation of lncRNA-miRNA-mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer. Biomedicines. 2022; 10(4). PMC: 9031843. DOI: 10.3390/biomedicines10040824. View

Tay Y, Rinn J, Pandolfi P . The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483):344-52. PMC: 4113481. DOI: 10.1038/nature12986. View

Quinn J, Chang H . Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2015; 17(1):47-62. DOI: 10.1038/nrg.2015.10. View

Morlando M, Fatica A . Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer. Int J Mol Sci. 2018; 19(2). PMC: 5855792. DOI: 10.3390/ijms19020570. View

Huang J, Chan W, Ngai C, Lok V, Zhang L, Lucero-Prisno 3rd D . Worldwide Burden, Risk Factors, and Temporal Trends of Ovarian Cancer: A Global Study. Cancers (Basel). 2022; 14(9). PMC: 9102475. DOI: 10.3390/cancers14092230. View

Lamouille S, Xu J, Derynck R . Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014; 15(3):178-96. PMC: 4240281. DOI: 10.1038/nrm3758. View

Chen Y, Gao D, Huang L . In vivo delivery of miRNAs for cancer therapy: challenges and strategies. Adv Drug Deliv Rev. 2014; 81:128-41. PMC: 5009470. DOI: 10.1016/j.addr.2014.05.009. View

Lee Y, Liao Y, Lu M, Hsieh P, Yu C . LINC00084/miR-204/ZEB1 Axis Mediates Myofibroblastic Differentiation Activity in Fibrotic Buccal Mucosa Fibroblasts: Therapeutic Target for Oral Submucous Fibrosis. J Pers Med. 2021; 11(8). PMC: 8398589. DOI: 10.3390/jpm11080707. View

Li N, Zhan X . Identification of clinical trait-related lncRNA and mRNA biomarkers with weighted gene co-expression network analysis as useful tool for personalized medicine in ovarian cancer. EPMA J. 2019; 10(3):273-290. PMC: 6695468. DOI: 10.1007/s13167-019-00175-0. View

10.

Wang X, Lai Q, He J, Li Q, Ding J, Lan Z . LncRNA SNHG6 promotes proliferation, invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF1 and inducing EMT via regulation of ZEB1. Int J Med Sci. 2019; 16(1):51-59. PMC: 6332483. DOI: 10.7150/ijms.27359. View

11.

Wang H, Niu L, Jiang S, Zhai J, Wang P, Kong F . Comprehensive analysis of aberrantly expressed profiles of lncRNAs and miRNAs with associated ceRNA network in muscle-invasive bladder cancer. Oncotarget. 2016; 7(52):86174-86185. PMC: 5349905. DOI: 10.18632/oncotarget.13363. View

12.

Skorda A, Bay M, Hautaniemi S, Lahtinen A, Kallunki T . Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises. Cancers (Basel). 2022; 14(24). PMC: 9777107. DOI: 10.3390/cancers14246257. View

13.

Chen X, Yang Y, Sun J, Hu C, Ge X, Li R . LncRNA HCG11 represses ovarian cancer cell growth via AKT signaling pathway. J Obstet Gynaecol Res. 2022; 48(3):796-805. DOI: 10.1111/jog.15083. View

14.

Richards E, Zhang G, Li Z, Permuth-Wey J, Challa S, Li Y . Long non-coding RNAs (LncRNA) regulated by transforming growth factor (TGF) β: LncRNA-hit-mediated TGFβ-induced epithelial to mesenchymal transition in mammary epithelia. J Biol Chem. 2015; 290(11):6857-67. PMC: 4358111. DOI: 10.1074/jbc.M114.610915. View

15.

Zhang H, Cai K, Wang J, Wang X, Cheng K, Shi F . MiR-7, inhibited indirectly by lincRNA HOTAIR, directly inhibits SETDB1 and reverses the EMT of breast cancer stem cells by downregulating the STAT3 pathway. Stem Cells. 2014; 32(11):2858-68. DOI: 10.1002/stem.1795. View

16.

Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M . A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 2011; 147(2):358-69. PMC: 3234495. DOI: 10.1016/j.cell.2011.09.028. View

17.

Torre L, Trabert B, DeSantis C, Miller K, Samimi G, Runowicz C . Ovarian cancer statistics, 2018. CA Cancer J Clin. 2018; 68(4):284-296. PMC: 6621554. DOI: 10.3322/caac.21456. View

18.

Wang Q, Wang L, Zhang C, Bai N, Feng C, Zhang Z . LncRNA CRNDE promotes cell proliferation, migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis. Mol Cell Biochem. 2022; 477(5):1477-1488. DOI: 10.1007/s11010-022-04382-8. View

19.

Somasegar S, Reddy R, Chow S, Dorigo O, Renz M, Karam A . Trends in ovarian, fallopian tube, and primary peritoneal cancer incidence, mortality, and survival: A 15-year population-based analysis. Gynecol Oncol. 2024; 184:190-197. DOI: 10.1016/j.ygyno.2024.01.034. View

20.

Cai M, Wang Z, Zhang J, Zhou H, Jin L, Bai R . Adam17, a Target of Mir-326, Promotes Emt-Induced Cells Invasion in Lung Adenocarcinoma. Cell Physiol Biochem. 2015; 36(3):1175-85. DOI: 10.1159/000430288. View