Abstract
ABSTRACTLncRNA 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.
Highlights
Human papillomavirus (HPV) vaccines are available and effective screening methods have been established to reduce the incidence and mortality, cervical cancer (CC) remains the second most common cancer and third leading cause of death from cancer among females in developing countries [1]
LncRNA Malat1 up-regulation has been identified in a broad spectrum of tumor types [14,15,16], and its level may be even higher in the metastatic lesions compared with the primary tumor [17]
To study the impact of LINP1 on radiotherapy efficiency, we knocked down LINP1 using small interfering RNA in Hela S3 cells (Figure 4(a)) and generated cells stably expressing control or LINP1 shRNA by performing short hairpin RNA lentiviral transduction (Figure 4(b))
Summary
Human papillomavirus (HPV) vaccines are available and effective screening methods have been established to reduce the incidence and mortality, cervical cancer (CC) remains the second most common cancer and third leading cause of death from cancer among females in developing countries [1]. Treatment of cervical cancer may vary within some combination of surgery, chemotherapy, radiotherapy and targeted therapy, depending mainly on the individual stages defined by Federation Internationale de Gynecologie et d’Obstetrique (FIGO). LncRNA Malat (metastasis-associated lung adenocarcinoma transcript 1) up-regulation has been identified in a broad spectrum of tumor types [14,15,16], and its level may be even higher in the metastatic lesions compared with the primary tumor [17]. Considering the importance of LINP1 in DNA damage repair progression and the possibility it may help to classify radioresistant tumors and serve as a treatment target, we investigated its expression and functions in cervical cancers
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