Department of Gynaecology, Shaanxi Provincial People's Hospital, Xi'an, China.
Environ Toxicol. 2022 Jan;37(1):161-170. doi: 10.1002/tox.23387. Epub 2021 Oct 15.
Long non-coding RNA (lncRNA) LINC00514 is a cancer-related lncRNA that has been proven to be implicated in the progression of several cancers. However, the biological function of LINC00514 in cervical squamous cell carcinoma (CSCC) remains unclear. Thus, we aimed to identify the LINC00514 expression profile in CSCC and determine its exact mechanism. Our results showed that the expression of LINC00514 was up-regulated in human CSCC tissues and cell lines. Knockdown of LINC00514 significantly inhibited the proliferation and invasion of CSCC cells, as well as suppressed tumorigenesis of CSCC in vivo. In addition, LINC00514 was found to work as a miRNA sponge for miR-708-5p and suppressed the expression of miR-708-5p in CSCC cells. Homeobox B3 (HOXB3) was found to be a target gene of miR-708-5p. Rescue assays demonstrated that miR-708-5p inhibitor attenuated the effects of LINC00514 knockdown on cell proliferation and invasion in CSCC cells. In addition, overexpression of HOXB3 reversed the inhibitory effects of miR-708-5p mimics on cell proliferation and invasion. Taken together, our findings for the first time elucidated that lncRNA LINC00514 promotes the proliferation and invasion through the miR-708-5p/HOXB3 axis in CSCC. Thus, LINC00514/miR-708-5p/HOXB3 axis might be a promising therapeutic target for the treatment of CSCC.
长链非编码 RNA (lncRNA) LINC00514 是一种与癌症相关的 lncRNA,已被证明与几种癌症的进展有关。然而,LINC00514 在宫颈鳞状细胞癌 (CSCC) 中的生物学功能仍不清楚。因此,我们旨在确定 LINC00514 在 CSCC 中的表达谱,并确定其确切机制。
我们的研究结果表明,LINC00514 在人 CSCC 组织和细胞系中表达上调。敲低 LINC00514 显著抑制 CSCC 细胞的增殖和侵袭,并抑制 CSCC 的体内致瘤性。此外,发现 LINC00514 作为 miR-708-5p 的 miRNA 海绵,并抑制 CSCC 细胞中 miR-708-5p 的表达。发现同源盒 B3 (HOXB3) 是 miR-708-5p 的靶基因。
挽救实验表明,miR-708-5p 抑制剂减弱了 LINC00514 敲低对 CSCC 细胞增殖和侵袭的影响。此外,HOXB3 的过表达逆转了 miR-708-5p 模拟物对细胞增殖和侵袭的抑制作用。
总之,我们的研究结果首次阐明,lncRNA LINC00514 通过 miR-708-5p/HOXB3 轴促进 CSCC 的增殖和侵袭。因此,LINC00514/miR-708-5p/HOXB3 轴可能是治疗 CSCC 的有前途的治疗靶点。