MicroRNA-769-3p Inhibits Tumor Progression in Glioma by Suppressing ZEB2 and Inhibiting the Wnt/β-catenin Signaling Pathway

Overview

Journal Oncol Lett

Specialty Oncology

Date 2020 Jan 4

PMID 31897212

Citations 15

Authors

Kai Wang

Shasha Yang

Yishen Gao

Caihong Zhang

Qiangbo Sui

Affiliations

Soon will be listed here.

Abstract

Accumulating evidence suggests the crucial role of microRNAs (miRNAs) in human cancers. The present study aimed to investigate the clinical and functional roles of miR-769-3p in glioma, as well as the underlying molecular mechanisms. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression levels of miR-769-3p in glioma tissues and cells. Receiver operating characteristic (ROC) curve analysis was applied to calculate the diagnostic value of miR-769-3p. The 5-year survival rate of patients was calculated using Kaplan-Meier analysis and Cox regression analysis. Cell experiments were used to investigate the functional role of miR-769-3p in glioma. The gene target of miR-769-3p was predicted by TargetScan. Changes in the levels of Wnt signaling-related proteins were measured by western blotting. miR-769-3p was significantly downregulated in glioma tissues and serum, as well as in glioma cell lines (P<0.001). miR-769-3p expression was significantly associated with the World Health Organization grade and Karnofsky performance score. The ROC curves demonstrated that serum miR-769-3p level reliably distinguished patients with glioma from healthy individuals. High tissue miR-769-3p expression predicted poor overall survival in patients with glioma (log-rank P=0.001) and was identified as an independent prognostic factor. In addition, zinc finger E-box binding homeobox 2 (ZEB2) was demonstrated to be a direct target of miR-769-3p in glioma cells using a luciferase assay. miR-769-3p upregulation suppressed the activity of the Wnt/β-catenin signaling pathway in glioma cells. In conclusion, miR-769-3p may serve as a diagnostic and prognostic biomarker in patients with glioma and target ZEB2 to inhibit tumor progression via the Wnt/β-catenin signaling pathway. miR-769-3p may be a novel therapeutic target for the treatment of glioma.

Citing Articles

ZEB2 reduction contributes to pre-eclampsia via Wnt/β-Catenin pathway.

Zhang Y, Gu F, Liu Y, Sun Y, Zhang L, Lu D Cell Div. 2024; 19(1):34.

PMID: 39614362 PMC: 11607827. DOI: 10.1186/s13008-024-00137-7.

miR-769-3p inhibits cellular proliferation of KSHV-infected SH-SY5Y cells through targeting mTOR.

Cao D, Wu Z, Yang R, Yao L, Huang J, Ding Y J Cancer. 2024; 15(11):3338-3349.

PMID: 38817860 PMC: 11134426. DOI: 10.7150/jca.93595.

Zinc Finger E-Box Binding Homeobox Family: Non-Coding RNA and Epigenetic Regulation in Gliomas.

Lenda B, Zebrowska-Nawrocka M, Turek G, Balcerczak E Biomedicines. 2023; 11(5).

PMID: 37239035 PMC: 10216372. DOI: 10.3390/biomedicines11051364.

In silico Identification of Hypoxic Signature followed by reverse transcription-quantitative PCR Validation in Cancer Cell Lines.

Shayan S, Bahramali G, Arashkia A, Azadmanesh K Iran Biomed J. 2023; 27(1):23-33.

PMID: 36624663 PMC: 9971715. DOI: 10.52547/ibj.3803.

Identification of a novel miRNA-based recurrence and prognosis prediction biomarker for hepatocellular carcinoma.

Zhang X, Zhang D, Bu X, Zhang X, Cui L BMC Bioinformatics. 2022; 23(1):479.

PMID: 36376850 PMC: 9664787. DOI: 10.1186/s12859-022-05040-y.

References

Li Y, Zhang J, Zhang W, Liu Y, Li Y, Wang K . MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1. J Mol Histol. 2017; 48(5-6):357-366. DOI: 10.1007/s10735-017-9734-3. View

Huang S, Zheng S, Huang S, Cheng H, Lin Y, Wen Y . Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma. Artif Cells Nanomed Biotechnol. 2019; 47(1):250-255. DOI: 10.1080/21691401.2018.1549062. View

Chen X, Wang A . Clinical significance of miR-195 in hepatocellular carcinoma and its biological function in tumor progression. Onco Targets Ther. 2019; 12:527-534. PMC: 6330974. DOI: 10.2147/OTT.S190108. View

Wang Y, Yang Q, Cheng Y, Gao M, Kuang L, Wang C . Myosin Heavy Chain 10 (MYH10) Gene Silencing Reduces Cell Migration and Invasion in the Glioma Cell Lines U251, T98G, and SHG44 by Inhibiting the Wnt/β-Catenin Pathway. Med Sci Monit. 2018; 24:9110-9119. PMC: 6319164. DOI: 10.12659/MSM.911523. View

Wu Y, Ou C, Chien P, Chang H, Ko J, Wang B . Chidamide-induced ROS accumulation and miR-129-3p-dependent cell cycle arrest in non-small lung cancer cells. Phytomedicine. 2019; 56:94-102. DOI: 10.1016/j.phymed.2018.09.218. View

Komori T . The 2016 WHO Classification of Tumours of the Central Nervous System: The Major Points of Revision. Neurol Med Chir (Tokyo). 2017; 57(7):301-311. PMC: 5566703. DOI: 10.2176/nmc.ra.2017-0010. View

Ostrom Q, Bauchet L, Davis F, Deltour I, Fisher J, Langer C . The epidemiology of glioma in adults: a "state of the science" review. Neuro Oncol. 2014; 16(7):896-913. PMC: 4057143. DOI: 10.1093/neuonc/nou087. View

Gong X, Liao X, Huang M . LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway. Pathol Res Pract. 2019; 215(3):564-570. DOI: 10.1016/j.prp.2019.01.018. View

Zhang X, Xu X, Ge G, Zang X, Shao M, Zou S . miR‑498 inhibits the growth and metastasis of liver cancer by targeting ZEB2. Oncol Rep. 2018; 41(3):1638-1648. PMC: 6365765. DOI: 10.3892/or.2018.6948. View

10.

Ju Q, Zhao L, Gao J, Zhou L, Xu Y, Sun Y . Mutant p53 increases exosome-mediated transfer of miR-21-3p and miR-769-3p to promote pulmonary metastasis. Chin J Cancer Res. 2019; 31(3):533-546. PMC: 6613506. DOI: 10.21147/j.issn.1000-9604.2019.03.15. View

11.

Wang R, Zuo X, Wang K, Han Q, Zuo J, Ni H . MicroRNA-485-5p attenuates cell proliferation in glioma by directly targeting paired box 3. Am J Cancer Res. 2019; 8(12):2507-2517. PMC: 6325470. View

12.

Zhang W, Zhao W, Ge C, Li X, Yang X, Xiang Y . Decreased let-7b is associated with poor prognosis in glioma. Medicine (Baltimore). 2019; 98(22):e15784. PMC: 6709123. DOI: 10.1097/MD.0000000000015784. View

13.

Qiu H, Lu X, Yang S, Weng C, Zhang E, Chen F . MiR-769 promoted cell proliferation in human melanoma by suppressing GSK3B expression. Biomed Pharmacother. 2016; 82:117-23. DOI: 10.1016/j.biopha.2016.04.052. View

14.

Zhang C, Du H . Screening key miRNAs for human hepatocellular carcinoma based on miRNA-mRNA functional synergistic network. Neoplasma. 2017; 64(6):816-823. DOI: 10.4149/neo_2017_602. View

15.

Zhang F, Wu A, Wang Y, Liu J . miR-490-3p functions as a tumor suppressor in glioma by inhibiting high-mobility group AT-hook 2 expression. Exp Ther Med. 2019; 18(1):664-670. PMC: 6566118. DOI: 10.3892/etm.2019.7606. View

16.

Epifanova E, Babaev A, Newman A, Tarabykin V . Role of Zeb2/Sip1 in neuronal development. Brain Res. 2018; 1705:24-31. DOI: 10.1016/j.brainres.2018.09.034. View

17.

Suzuki K, Kawataki T, Endo K, Miyazawa K, Kinouchi H, Saitoh M . Expression of ZEBs in gliomas is associated with invasive properties and histopathological grade. Oncol Lett. 2018; 16(2):1758-1764. PMC: 6036434. DOI: 10.3892/ol.2018.8852. View

18.

Lima F, Assad Kahn S, Soletti R, Biasoli D, Alves T, da Fonseca A . Glioblastoma: therapeutic challenges, what lies ahead. Biochim Biophys Acta. 2012; 1826(2):338-49. DOI: 10.1016/j.bbcan.2012.05.004. View

19.

Ji H, Sang M, Liu F, Ai N, Geng C . miR-124 regulates EMT based on ZEB2 target to inhibit invasion and metastasis in triple-negative breast cancer. Pathol Res Pract. 2019; 215(4):697-704. DOI: 10.1016/j.prp.2018.12.039. View

20.

Waghmare I, Roebke A, Minata M, Kango-Singh M, Nakano I . Intercellular cooperation and competition in brain cancers: lessons from Drosophila and human studies. Stem Cells Transl Med. 2014; 3(11):1262-8. PMC: 4214844. DOI: 10.5966/sctm.2014-0086. View