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通过抑制LASP1,长链非编码RNA LINC01123的敲低在miR-625-5p上起到分子海绵的作用,从而抑制结直肠癌细胞的进程。

Knockdown of long non-coding RNA LINC01123 plays a molecular sponge on miR-625-5p to inhibit the process of colorectal cancer cells via LASP1.

发表日期:2023 Sep 07
作者: Tao Shang, Shikai Pang, Yunfei Dong
来源: Disease Models & Mechanisms

摘要:

大肠癌(CRC)在癌症晚期时,其5年生存率较低。对CRC分子生物学机制的研究对疾病预防和治疗具有帮助。长链非编码RNA(lncRNA)被证明是CRC治疗靶点的合适选择。我们研究小组此前发现,LINC01123通过调控miR-625-5p和LIM和SH3蛋白1(LASP1)促进CRC的增殖和转移。因此,本研究推测LINC01123对miR-625-5p的分子海绵效应通过调控LASP1影响了CRC的过程。我们通过建立LINC01123沉默的CRC细胞模型(使用LOVO和SW480细胞)和异种移植瘤模型来验证上述假设。结果发现,沉默LINC01123抑制了LOVO和SW480细胞的存活能力、增殖、转移和侵袭,但促进了细胞凋亡。此外,LINC01123的沉默在体外抑制了LASP1、N-钙黏附蛋白、PCNA和Bcl-2蛋白水平,并提高了E-钙黏附蛋白、Bax和Caspase-3蛋白水平。此外,研究还表明LINC01123作为一种分子海绵靶向miR-625-5p/LASP1轴。异种移植瘤实验的结果进一步验证了LINC01123沉默对体内肿瘤生长的影响。而miR-625-5p模拟物处理促进了LINC01123沉默对CRC细胞的上述效应,而过表达LASP1对LINC01123沉默有拮抗效应。总之,本研究表明LINC01123的沉默通过对miR-625-5p/LASP1轴的调控抑制了CRC的过程。这一发现有望为CRC的生物学机制研究提供研究基础。© 2023. 作者,独家许可给 Springer Nature B.V.
Colorectal cancer (CRC) at an advanced stage of cancer has a lower 5-year survival rate. Research on the molecular biological mechanisms of CRC is helpful for disease prevention and treatment. Long non-coding RNAs (lncRNAs) were shown to be suitable as therapeutic targets for CRC. Previously, our research team found that LINC01123 promoted proliferation and metastasis in CRC by regulating miR-625-5p and the LIM and SH3 protein 1 (LASP1). Therefore, this study speculated that the molecular sponge effect of LINC01123 on miR-625-5p affected the process of CRC via regulating LASP1. The LINC01123-silenced CRC cell models (using the LOVO and SW480 cells) and xenograft tumor models were established to verify the above conjecture. As a result, it was found that silencing LINC01123 inhibited viability, proliferation, metastasis, and invasion but promoted apoptosis in LOVO and SW480 cells. Additionally, the knockdown of LINC01123 inhibited the LASP1, N-cadherin, PCNA, and Bcl-2 protein levels and raised the E-cadherin, Bax, and Caspase-3 protein levels in vitro. Furthermore, it showed that LINC01123, as a molecular sponge, targeted the miR-625-5p/LASP1 axis. The results of the xenograft tumor assay further verified the above effects of LINCO1123-silenced on tumor growth in vivo. And the miR-625-5p mimics treatment promoted the aforementioned effects of silencing LINC01123 on CRC cells while overexpressing LASP1 has an antagonistic effect to silencing LINC01123. In conclusion, this study suggests that silencing LINC01123 inhibits the process of CRC via sponging to the miR-625-5p/LASP1 axis. This finding hopes to provide research fundamentals on the biological mechanism study of CRC.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.