Medical College of Guizhou University, Guiyang 550025, Guizhou, P.R. China.
Department of Gynaecology, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou, P.R. China.
Biochem Cell Biol. 2020 Oct;98(5):591-599. doi: 10.1139/bcb-2019-0446. Epub 2020 Apr 29.
There is a growing body of evidence indicating that long non-coding RNAs (lncRNAs) are associated with a variety of cancers. LncRNA LINP1 has been shown to be a key factor in tumor malignancy. However, the role of LINP1 in cervical cancer (CC) it is unclear. In our research, we found that the levels of LINP1 were significantly elevated in CC tissues by comparison with adjacent normal tissue. Further, the expression level of LINP1 was upregulated in CC cells compared with healthy human cervical epithelial cell lines (HUCEC). Surprisingly, we found that downregulation of LINP1 significantly reduced the proliferation of CC cells and promoted apoptosis. Additionally, downregulation of LINP1 significantly decreased CC tumor growth in vivo. Further, we observed that LINP1 recruits EZH2, LSD1, and DNMT1, thereby reducing the expression of KLF2 and PRSS8. The results from our qRT-PCR analyses showed that silencing LINP1 uprgulated the expression of KLF2 and PRSS8 in CC cells. The results from our loss-of-function assays showed that upregulation of KLF2 and PRSS8 inhibits cell proliferation and boosts cell apoptosis in CC. We also found that inhibition of KLF2 and PRSS8 reversed the inhibitory effect on cell proliferation associated with silencing LINP1. In short, LINP1 facilitates the progression of CC by suppressing KLF2 and PRSS8, and thus could provide a promising target for CC therapy.
越来越多的证据表明，长非编码 RNA（lncRNA）与多种癌症有关。lncRNA LINP1 已被证明是肿瘤恶性的关键因素。然而，LINP1 在宫颈癌（CC）中的作用尚不清楚。在我们的研究中，通过与相邻正常组织相比，发现 CC 组织中 LINP1 的水平显着升高。此外，与健康人宫颈上皮细胞系（HUCEC）相比，CC 细胞中 LINP1 的表达水平上调。令人惊讶的是，我们发现下调 LINP1 显着降低了 CC 细胞的增殖并促进了细胞凋亡。此外，下调 LINP1 显着减少了体内 CC 肿瘤的生长。此外，我们观察到 LINP1 募集了 EZH2、LSD1 和 DNMT1，从而降低了 KLF2 和 PRSS8 的表达。我们的 qRT-PCR 分析结果表明，沉默 LINP1 上调了 CC 细胞中 KLF2 和 PRSS8 的表达。我们的功能丧失测定结果表明，上调 KLF2 和 PRSS8 抑制了 CC 中的细胞增殖并促进了细胞凋亡。我们还发现，抑制 KLF2 和 PRSS8 逆转了沉默 LINP1 与细胞增殖抑制相关的抑制作用。简而言之，LINP1 通过抑制 KLF2 和 PRSS8 促进 CC 的进展，因此可能为 CC 治疗提供有希望的靶标。
