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微小RNA-429通过抑制Wnt/β-连环蛋白信号通路靶向同源盒A9来抑制骨肉瘤进展。

miR-429 inhibits osteosarcoma progression by targeting HOXA9 through suppressing Wnt/β-catenin signaling pathway.

作者信息

Sun Liangzhi, Wang Libo, Luan Suxian, Jiang Yanzhou, Wang Qiang

机构信息

Department of Orthopedics, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China.

Hetan Health Center, Weifang, Shandong 261100, P.R. China.

出版信息

Oncol Lett. 2020 Sep;20(3):2447-2455. doi: 10.3892/ol.2020.11766. Epub 2020 Jun 24.

DOI:10.3892/ol.2020.11766
PMID:32782562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7399823/
Abstract

Osteosarcoma (OS) is the most commonly diagnosed malignant cancer of bone that occurs in adolescents and children. Mounting number of studies have indicated that miRNAs are increasingly playing fundamental roles in OS development. Thus, the biological function of miR-429 in OS progression was explored. The results of RT-qPCR revealed that miR-429 was downregulated in OS tissues and OS cell lines (MG-63, U2OS, Saos-2) while homeobox A9 (HOXA9) was markedly increased. Moreover, HOXA9 was confirmed as a direct target of miR-429 by using luciferase reporter assay. It was identified that miR-429 exhibited a suppressive effect on OS progression while HOXA9 showed the oncogenic function in OS progression by using MTT and Transwell assays. More importantly, rescue assays manifested that HOXA9 can partially overturn the suppressive effect of miR-429 on OS. Overexpression of miR-429 inhibited the activation of Wnt/β-catenin signaling pathway. In conclusion, miR-429 suppressed OS progression by targeting HOXA9 through Wnt/β-catenin pathway.

摘要

骨肉瘤（OS）是青少年和儿童中最常被诊断出的原发性恶性骨肿瘤。越来越多的研究表明，微小RNA（miRNA）在骨肉瘤的发生发展中发挥着重要作用。因此，本研究探讨了miR-429在骨肉瘤进展中的生物学功能。RT-qPCR结果显示，miR-429在骨肉瘤组织和骨肉瘤细胞系（MG-63、U2OS、Saos-2）中表达下调，而同源框A9（HOXA9）表达显著上调。此外，荧光素酶报告基因实验证实HOXA9是miR-429的直接靶点。MTT实验和Transwell实验结果表明，miR-429对骨肉瘤进展具有抑制作用，而HOXA9则发挥致癌作用。更重要的是，挽救实验表明HOXA9可部分逆转miR-429对骨肉瘤的抑制作用。miR-429过表达抑制了Wnt/β-连环蛋白信号通路的激活。综上所述，miR-429通过靶向HOXA9调控Wnt/β-连环蛋白信号通路，从而抑制骨肉瘤进展。

相似文献

[1]
miR-429 inhibits osteosarcoma progression by targeting HOXA9 through suppressing Wnt/β-catenin signaling pathway.

Oncol Lett. 2020-9

[2]
MicroRNA-182 downregulates Wnt/β-catenin signaling, inhibits proliferation, and promotes apoptosis in human osteosarcoma cells by targeting HOXA9.

Oncotarget. 2017-9-22

[3]
MicroRNA-1294 targets HOXA9 and has a tumor suppressive role in osteosarcoma.

Eur Rev Med Pharmacol Sci. 2018-12

[4]
miR-196 acts as a tumor suppressor in osteosarcoma by targeting HOXA9.

Int J Clin Exp Pathol. 2018-9-1

[5]
Down-regulation of microRNA-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/β-catenin signaling pathway by enhancing AXIN1.

Exp Mol Pathol. 2019-3-4

[6]
MicroRNA‑873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt/β‑catenin pathway.

Int J Oncol. 2019-2-28

[7]
Sevoflurane Inhibited Osteosarcoma Cell Proliferation And Invasion Via Targeting miR-203/WNT2B/Wnt/β-Catenin Axis.

Cancer Manag Res. 2019-11-11

[8]
microRNA-758 inhibits the malignant phenotype of osteosarcoma cells by directly targeting and deactivating the Wnt/β-catenin pathway.

Am J Cancer Res. 2019-1-1

[9]
Overexpressing circular RNA hsa_circ_0002052 impairs osteosarcoma progression via inhibiting Wnt/β-catenin pathway by regulating miR-1205/APC2 axis.

Biochem Biophys Res Commun. 2018-6-5

[10]
MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway.

World J Surg Oncol. 2021-8-20

引用本文的文献

[1]
miRNA Expression Patterns in Early- and Late-Stage Prostate Cancer Patients: High-Throughput Analysis.

Biomedicines. 2023-11-16

[2]
Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies.

MedComm (2020). 2023-7-10

[3]
HIF-1-Induced hsa-miR-429: Understanding Its Direct Targets as the Key to Developing Cancer Diagnostics and Therapies.

Cancers (Basel). 2023-5-25

[4]
Hsa_circ_0084912 Drives the Progression of Cervical Cancer Via Regulating miR-429/SOX2 Pathway.

Mol Biotechnol. 2023-12

[5]
Role of HOXA9 in solid tumors: mechanistic insights and therapeutic potential.

Cancer Cell Int. 2022-11-14

[6]
The role of miR-200 family in the regulation of hallmarks of cancer.

Front Oncol. 2022-9-8

[7]
Mir-34a: a regulatory hub with versatile functions that controls osteosarcoma networks.

Cell Cycle. 2022-10

[8]
CircRNA FUT10 regulates the regenerative potential of aged skeletal muscle stem cells by targeting HOXA9.

Aging (Albany NY). 2021-7-13

[9]
Osteosarcoma Pathogenesis Leads the Way to New Target Treatments.

Int J Mol Sci. 2021-1-15

[10]
Downregulation of microRNA-605 indicates poor prognosis and promotes the progression of osteosarcoma.

Oncol Lett. 2020-12

本文引用的文献

[1]
MicroRNA-429 inhibits cancer cell proliferation and migration by targeting AKT1 in renal cell carcinoma.

Mol Clin Oncol. 2020-1

[2]
The effects of miR-429 on cell migration and invasion by targeting Slug in esophageal squamous cell carcinoma.

Pathol Res Pract. 2019-7-12

[3]
MicroRNA-429 inhibits cancer cell proliferation and migration by targeting the AKT1 in melanoma.

Cancer Biomark. 2019

[4]
Genome-wide DNA methylation profile of early-onset endometrial cancer: its correlation with genetic aberrations and comparison with late-onset endometrial cancer.

Carcinogenesis. 2019-7-4

[5]
miR-429 suppresses cell growth and induces apoptosis of human thyroid cancer cell by targeting ZEB1.

Artif Cells Nanomed Biotechnol. 2019-12

[6]
MicroRNA‑873 targets HOXA9 to inhibit the aggressive phenotype of osteosarcoma by deactivating the Wnt/β‑catenin pathway.

Int J Oncol. 2019-2-28

[7]
miR-195-5p/NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization.

J Hematol Oncol. 2019-2-26

[8]
Delivery of Liver-Specific miRNA-122 Using a Targeted Macromolecular Prodrug toward Synergistic Therapy for Hepatocellular Carcinoma.

ACS Appl Mater Interfaces. 2019-3-8

[9]
Recombinant cell-permeable HOXA9 protein inhibits NSCLC cell migration and invasion.

Cell Oncol (Dordr). 2019-1-29

[10]
Delta tocotrienol in recurrent ovarian cancer. A phase II trial.

Pharmacol Res. 2019-1-9

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