The 5th Ward of Radiotherapy Department of Affiliated Cancer Hospital, Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.
The 3rd Ward of Radiotherapy Department of Affiliated Cancer Hospital, Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.
J Cell Physiol. 2020 Oct;235(10):7592-7603. doi: 10.1002/jcp.29667. Epub 2020 Apr 23.
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.
宫颈癌（CC）是女性中最常见的恶性肿瘤之一，发病率和死亡率都很高。尽管在诊断和治疗策略方面取得了令人鼓舞的进展，但仍需要有效的治疗策略和对 CC 发病机制的进一步探索。我们检索了癌症基因组图谱数据库，发现长非编码 RNA LINC02535 在 CC 中高度表达。LINC02535 在 CC 中尚未被研究，其分子调控机制尚不清楚。基于 starBase 数据库，LINC02535 可能与聚（rC）结合蛋白 2（PCBP2）结合。在本研究中，我们发现与相邻正常组织和正常宫颈上皮细胞相比，CC 组织和细胞中 LINC02535 和 PCBP2 的表达显著增加。LINC02535 和 PCBP2 可以相互结合，并位于细胞质中。LINC02535 和 PCBP2 促进 CC 中的细胞增殖、迁移、侵袭，并抑制细胞凋亡。LINC02535 和 PCBP2 促进 DNA 损伤的修复，促进 CC 的进展。LINC02535 与 PCBP2 合作增强 RRM1 信使 RNA（mRNA）的稳定性。RRM1 促进了 CC 细胞中 DNA 损伤的修复和上皮间质转化（EMT）过程。LINC02535 在体内调节肿瘤发生。总之，LINC02535 与 PCBP2 合作，通过促进 DNA 损伤的修复来调节 RRM1 mRNA 的稳定性，从而促进 CC 细胞的增殖和 EMT 过程，为 CC 提供了一个潜在的生物标志物。
