LINP1 facilitates DNA damage repair through non-homologous end joining (NHEJ) pathway and subsequently decreases the sensitivity of cervical cancer cells to ionizing radiation

Xuanxuan Wang; Hai Liu; Liming Shi; Xiaoli Yu; Yanjun Gu; Xiaonan Sun

doi:10.1080/15384101.2018.1442625

LINP1 facilitates DNA damage repair through non-homologous end joining (NHEJ) pathway and subsequently decreases the sensitivity of cervical cancer cells to ionizing radiation

Cell Cycle. 2018;17(4):439-447. doi: 10.1080/15384101.2018.1442625. Epub 2018 Apr 3.

Authors

Xuanxuan Wang¹, Hai Liu¹, Liming Shi¹, Xiaoli Yu², Yanjun Gu¹, Xiaonan Sun¹

Affiliations

¹ a Department of Radiation Oncology , Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University , Hangzhou , China.
² b Department of Pathology , Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University , Hangzhou , China.

Abstract

LncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1) is an lncRNA which promotes therapeutic resistance in triple-negative breast cancer (TNBC). However, the expression and function of LINP1 in cervical cancer is not yet well-understood. In this study, we evaluated the expression levels of LINP1 in tumor tissues and cell lines of cervical cancer. We found that LINP1 associates with NHEJ proteins (Ku80 and DNA-PKcs). LINP1 translocates from cytosol to nucleus in response to irradiation. In addition, LINP1 knockdown significantly increases the levels of cleaved caspase3 and PARP, leading to enhanced cell apoptosis after ionizing radiation (IR). LINP1-knockdown cells showed delayed repairs of DNA double-strand breaks (DSBs) after IR. Finally, LINP1 knockdown increases radiosensitivity of Hela S3 cells. These results suggest that LINP1 facilitates DSBs repair through NHEJ pathway and may thus serve as a prognostic marker and a potential target for the therapy of cervical cancer.

Keywords: LINP1; cervical cancer; long non-coding RNA; radiation resistance; radiotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Calcium-Binding Proteins / metabolism
DNA End-Joining Repair / radiation effects
DNA Repair / radiation effects*
Female
HeLa Cells
Humans
Ku Autoantigen / metabolism
RNA Interference
RNA, Long Noncoding / antagonists & inhibitors
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
RNA, Small Interfering / metabolism
Radiation, Ionizing*
Uterine Cervical Neoplasms / metabolism
Uterine Cervical Neoplasms / pathology
Uterine Cervical Neoplasms / radiotherapy*

Substances

CIB1 protein, human
Calcium-Binding Proteins
LINP1 non-coding RNA, human
RNA, Long Noncoding
RNA, Small Interfering
Ku Autoantigen

Grants and funding

Natural Science Foundation of Zhejiang Province (CN) [grant number LY14H160016] Major Science and Technology Program of Zhejiang Province [grant number 2013C03044-6] Chinese National Natural Science Foundation [grant number 81441086, 81672976].