Long Noncoding RNA LINC02582 Acts Downstream of MiR-200c to Promote Radioresistance Through CHK1 in Breast Cancer Cells

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2019 Oct 12

PMID 31601781

Citations 45

Authors

Baiyao Wang

Jieling Zheng

Rong Li

Yunhong Tian

Jie Lin

Yingying Liang

Quanquan Sun

Anan Xu

Ronghui Zheng

Mengzhong Liu

Aimin Ji

Junguo Bu

Yawei Yuan

Affiliations

Soon will be listed here.

Abstract

Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.

Citing Articles

MicroRNA-200c in Cancer Generation, Invasion, and Metastasis.

Guo H, Zhang N, Huang T, Shen N Int J Mol Sci. 2025; 26(2).

PMID: 39859424 PMC: 11766322. DOI: 10.3390/ijms26020710.

Radioresistance and brain metastases: a review of the literature and applied perspective.

Youssef A, Sahgal A, Das S Front Oncol. 2024; 14:1477448.

PMID: 39540151 PMC: 11557554. DOI: 10.3389/fonc.2024.1477448.

Exploring the clinical potential of circulating LncRNAs in breast cancer: insights into primary signaling pathways and therapeutic interventions.

Al-Noshokaty T, Abdelhamid R, Reda T, Alaaeldien A, Abdellatif N, Mansour A Funct Integr Genomics. 2024; 24(6):209.

PMID: 39508907 DOI: 10.1007/s10142-024-01476-y.

Loss of miR-200c-3p promotes resistance to radiation therapy via the DNA repair pathway in prostate cancer.

Labbe M, Chang M, Saintpierre B, Letourneur F, de Beaurepaire L, Veziers J Cell Death Dis. 2024; 15(10):751.

PMID: 39414799 PMC: 11484813. DOI: 10.1038/s41419-024-07133-3.

Non-coding RNAs as modulators of radioresponse in triple-negative breast cancer: a systematic review.

Tofolo M, Berti F, Nunes-Souza E, Ruthes M, Berti L, Fonseca A J Biomed Sci. 2024; 31(1):93.

PMID: 39354523 PMC: 11445946. DOI: 10.1186/s12929-024-01081-y.

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