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长链非编码RNA LINC01123的敲低通过LASP1对miR-625-5p起分子海绵作用,以抑制结肠癌细胞的进程。

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.

作者信息

Shang Tao, Pang Shikai, Dong Yunfei

机构信息

Anus-intestines Department, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310000, China.

Department of General Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310000, China.

出版信息

J Mol Histol. 2023 Oct;54(5):521-537. doi: 10.1007/s10735-023-10141-w. Epub 2023 Sep 7.

Abstract

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.

摘要

晚期结直肠癌(CRC)的5年生存率较低。对CRC分子生物学机制的研究有助于疾病的预防和治疗。长链非编码RNA(lncRNAs)被证明适合作为CRC的治疗靶点。此前,我们的研究团队发现LINC01123通过调控miR-625-5p和LIM与SH3结构域蛋白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CRC进程。构建了LINC01123沉默的CRC细胞模型(采用LOVO和SW480细胞)和异种移植肿瘤模型来验证上述推测。结果发现,沉默LINC01123可抑制LOVO和SW480细胞的活力、增殖、转移和侵袭,但促进细胞凋亡。此外,在体外敲低LINC01123可抑制LASP1、N-钙黏蛋白、增殖细胞核抗原(PCNA)和Bcl-2蛋白水平,并提高E-钙黏蛋白、Bax和半胱天冬酶-3蛋白水平。此外,研究表明LINC01123作为分子海绵靶向miR-625-5p/LASP1轴。异种移植肿瘤实验结果进一步验证了沉默LINC01123对体内肿瘤生长的上述作用。miR-625-5p模拟物处理可增强沉默LINC01123对CRC细胞的上述作用,而过表达LASP1对沉默LINC01123具有拮抗作用。总之,本研究表明沉默LINC01123通过作用于miR-625-5p/LASP1轴抑制CRC进程。这一发现有望为CRC生物学机制研究提供基础。

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