LINC02535 co‐functions with PCBP2 to regulate DNA damage repair in cervical cancer by stabilizing RRM1 mRNA

• Published in: Journal of cellular physiology Vol. 235; no. 10; pp. 7592 - 7603
• Main Authors: Wen, Danxia, Huang, Zhong, Li, Zhouyu, Tang, Xi, Wen, Xiaomin, Liu, Jinquan, Li, Mingyi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.10.2020
• Subjects: Animals; Apoptosis; Apoptosis - genetics; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Carcinogenesis - genetics; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Cervical cancer; Cervix; Cytoplasm; Damage; Deoxyribonucleic acid; Diagnostic systems; DNA; DNA damage; DNA Damage - genetics; DNA repair; DNA Repair - genetics; Epithelial cells; Epithelial Cells - pathology; Epithelial-Mesenchymal Transition - genetics; Female; Genomes; HeLa Cells; Humans; LINC02535; Mesenchyme; Mice; Mice, Inbred BALB C; Mice, Nude; Morbidity; mRNA stability; PCBP2; Repair; Ribonucleic acid; Ribonucleoside Diphosphate Reductase - genetics; RNA; RNA, Long Noncoding - genetics; RNA, Messenger - genetics; RNA-Binding Proteins - genetics; RRM1; Stability; Tumorigenesis; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; RRM1; cervical cancer; LINC02535; PCBP2
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.29667

Cervical cancer (CC) is one of the commonest malignant cancers among women with high morbidity and mortality. Despite encouraging advances had been found in diagnostic and therapeutic strategies, effective therapeutic strategy and further exploration of the mechanism underlying in CC is still needed. We searched The Cancer Genome Atlas database and found that long noncoding RNA LINC02535 was highly expressed in CC. LINC02535 has not been studied in CC, and its molecular regulation mechanism remains unknown. Based on starBase database, LINC02535 could potentially bind poly (rC) binding protein 2 (PCBP2). In the present study, we discovered a significant increase of the LINC02535 and PCBP2 expression in CC tissues and cells as compared with the adjacent normal tissues and normal cervical epithelial cells. LINC02535 and PCBP2 can bind with each other and were colocated in cytoplasm. LINC02535 and PCBP2 promoted cell proliferation, migration, invasion, and suppressed apoptosis in CC. LINC02535 and PCBP2 facilitated the repair of DNA damage to promote CC progression. LINC02535 cooperated with PCBP2 to enhance the stability of RRM1 messenger RNA (mRNA). RRM1 promoted the repair of DNA damage and epithelial‐to‐mesenchymal transition (EMT) process in CC cells. LINC02535 regulated tumorigenesis in vivo. In conclusion, LINC02535 cooperated with PCBP2, regulated stability of RRM1 mRNA to promote cell proliferation and EMT process in CC cells by facilitating the repair of DNA damage, providing a potential biomarker for CC. 1. LINC02535 and poly (rC) binding protein 2 (PCBP2) are upregulated, and LINC02535 binds with PCBP2 in CC. 2. LINC02535 and PCBP2 promote cell proliferation, migration, invasion, and inhibit apoptosis in CC. 3. LINC02535 cooperates with PCBP2 to enhance the stability of RRM1 messenger RNA.