MiR-1254 Induced by NESG1 Inactivates HDGF/DDX5-stimulated Nuclear Translocation of β-catenin and Suppresses NPC Metastasis

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2021 Mar 15

PMID 33718512

Citations 8

Authors

Chao Cheng

Wenmin Li

Xuemei Peng

Xiong Liu

Ziyan Zhang

Zhen Liu

Tongyuan Deng

Rongcheng Luo

Weiyi Fang

Xiaojie Deng

Affiliations

Soon will be listed here.

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Chinese and other Southeast Asians. We aimed to explore the precise mechanism for NESG1 in NPC for understanding the pathogenesis of NPC. Transwell, Boyden assays, and wounding healing were respectively performed for cell metastasis. The microRNA (miRNA) microarray and luciferase reporter assays were designed to clarify NESG1-modulated miRNAs and miR-1254-targeted protein. Western blotting assays examined the pathways regulated by miR-1254, the (Hepatoma-Derived Growth Factor) HDGF/DDX5 complex, and NESG1. The chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and co-immunoprecipitation (coIP) assays were used to explore the DNA-protein complex and protein-protein complex. NESG1 suppressed NPC migration and invasion via Wnt/β-catenin signaling. Further, miR-1254 was confirmed as a positive downstream modulator of NESG1 reducing metastatic abilities of NPC cells and . Transduction of HDGF significantly restored cell migration and invasion ability in miR-1254-overexpressing NPC cells. In clinical samples, miR-1254 expression was negatively correlated with HDGF and positively correlated with NESG1 expression. miR-1254 acts as an independent prognostic factor for NPC, which was induced by NESG1 to suppress NPC metastasis via inactivating Wnt/β-catenin pathway and its downstream EMT signals.

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References

Chen Z, Qiu S, Lu X . The expression and clinical significance of HDGF in osteosarcoma. Onco Targets Ther. 2015; 8:2509-17. PMC: 4574856. DOI: 10.2147/OTT.S91708. View

Zan Y, Wang B, Liang L, Deng Y, Tian T, Dai Z . MicroRNA-139 inhibits hepatocellular carcinoma cell growth through down-regulating karyopherin alpha 2. J Exp Clin Cancer Res. 2019; 38(1):182. PMC: 6498602. DOI: 10.1186/s13046-019-1175-2. View

Chen R, Zhang Y, Zhang X . MiR-1254 Functions as a Tumor Suppressor in Oral Squamous Cell Carcinoma by Targeting CD36. Technol Cancer Res Treat. 2019; 18:1533033819859447. PMC: 6691659. DOI: 10.1177/1533033819859447. View

Li B, Chen P, Wang J, Wang L, Ren M, Zhang R . MicroRNA-1254 exerts oncogenic effects by directly targeting RASSF9 in human breast cancer. Int J Oncol. 2018; 53(5):2145-2156. DOI: 10.3892/ijo.2018.4530. View

Zhou J, Liu X, Wang C, Wang D, Du J . Decreased expression of miR-1254 is associated with cancer aggressiveness and predicts poor outcome in cervical cancer. Eur Rev Med Pharmacol Sci. 2018; 22(10):2997-3001. DOI: 10.26355/eurrev_201805_15056. View

Deng X, Liu Z, Liu X, Fu Q, Deng T, Lu J . miR-296-3p Negatively Regulated by Nicotine Stimulates Cytoplasmic Translocation of c-Myc via MK2 to Suppress Chemotherapy Resistance. Mol Ther. 2018; 26(4):1066-1081. PMC: 6079479. DOI: 10.1016/j.ymthe.2018.01.023. View

Bartel D . MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136(2):215-33. PMC: 3794896. DOI: 10.1016/j.cell.2009.01.002. View

Liu Z, Li X, He X, Jiang Q, Xie S, Yu X . Decreased expression of updated NESG1 in nasopharyngeal carcinoma: its potential role and preliminarily functional mechanism. Int J Cancer. 2010; 128(11):2562-71. DOI: 10.1002/ijc.25595. View

Wang W, Shen X, Jia W, Huang D, Wang Y, Pan Y . The p53/miR-193a/EGFR feedback loop function as a driving force for non-small cell lung carcinoma tumorigenesis. Ther Adv Med Oncol. 2019; 11:1758835919850665. PMC: 6535738. DOI: 10.1177/1758835919850665. View

10.

Zhao J, Ma M, Ren H, Liu Z, Edelman M, Pan H . Anti-HDGF targets cancer and cancer stromal stem cells resistant to chemotherapy. Clin Cancer Res. 2013; 19(13):3567-76. PMC: 3707124. DOI: 10.1158/1078-0432.CCR-12-3478. View

11.

Lin X, Zuo S, Luo R, Li Y, Yu G, Zou Y . HBX-induced miR-5188 impairs FOXO1 to stimulate β-catenin nuclear translocation and promotes tumor stemness in hepatocellular carcinoma. Theranostics. 2019; 9(25):7583-7598. PMC: 6831466. DOI: 10.7150/thno.37717. View

12.

Trop-Steinberg S, Azar Y . Is Myc an Important Biomarker? Myc Expression in Immune Disorders and Cancer. Am J Med Sci. 2018; 355(1):67-75. DOI: 10.1016/j.amjms.2017.06.007. View

13.

Zhang Y, Li Z, Hao Q, Tan W, Sun J, Li J . The Cdk2-c-Myc-miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin. Cancer Res. 2019; 79(19):4896-4910. PMC: 7451049. DOI: 10.1158/0008-5472.CAN-19-0020. View

14.

Hann S . MYC cofactors: molecular switches controlling diverse biological outcomes. Cold Spring Harb Perspect Med. 2014; 4(9):a014399. PMC: 4143105. DOI: 10.1101/cshperspect.a014399. View

15.

Meyer N, Penn L . Reflecting on 25 years with MYC. Nat Rev Cancer. 2008; 8(12):976-90. DOI: 10.1038/nrc2231. View

16.

Quan X, Li X, Yin Z, Ren Y, Zhou B . p53/miR-30a-5p/ SOX4 feedback loop mediates cellular proliferation, apoptosis, and migration of non-small-cell lung cancer. J Cell Physiol. 2019; 234(12):22884-22895. DOI: 10.1002/jcp.28851. View

17.

Zhao M, Luo R, Liu Y, Gao L, Fu Z, Fu Q . miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN. Nat Commun. 2016; 7:11309. PMC: 4842991. DOI: 10.1038/ncomms11309. View

18.

Chen Y, Chan A, Le Q, Blanchard P, Sun Y, Ma J . Nasopharyngeal carcinoma. Lancet. 2019; 394(10192):64-80. DOI: 10.1016/S0140-6736(19)30956-0. View

19.

Tang W, Zhou W, Xiang L, Wu X, Zhang P, Wang J . The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer. Nat Commun. 2019; 10(1):663. PMC: 6368584. DOI: 10.1038/s41467-018-08225-3. View

20.

Chou S, Peng H, Mo K, Hsu Y, Wu G, Hsiao J . MicroRNA-486-3p functions as a tumor suppressor in oral cancer by targeting DDR1. J Exp Clin Cancer Res. 2019; 38(1):281. PMC: 6599238. DOI: 10.1186/s13046-019-1283-z. View