Traditional Chinese Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), Wuhan, Hubei, China.
Bioengineered. 2022 Jan;13(1):746-758. doi: 10.1080/21655979.2021.2012628.
Long non-coding RNAs (lncRNAs) are critical regulators of hepatocellular carcinoma (HCC) carcinogenesis and development. We aimed to identify the function of the lncRNA ASMTL-AS1 during HCC malignancy. The expression of ASMTL-AS1, miR-1343-3p, and LAMC1 (laminin subunit gamma 1) was assessed in HCC tissues and cells. Cell Counting Kit-8 (CCK8) and Transwell migration assays were performed to determine the effect of ASMTL-AS1 on HCC cell proliferation and migration. Cell apoptosis was identified by detecting Bax and Bcl-2 protein expression using Western blotting, and a xenograft assay was performed to investigate tumor growth . The interplay between miR-1343-3p and ASMTL-AS1 or LAMC1 was verified through luciferase reporter and RNA immunoprecipitation assays. ASMTL-AS1 and LAMC1 were highly expressed in HCC tissues and cells, whereas miR-1343-3p showed low expression. Clinically, miR-1343-3p expression in HCC tissues showed a negative correlation with ASMTL-AS1 or LAMC1 expression. Functional assays demonstrated that ASMTL-AS1 silencing suppressed HCC cell proliferation and migration and increased cell apoptosis. More interestingly, ASMTL-AS1 sponged miR-1343-3p and miR-1343-3p to target the 3'-UTR of LAMC1, thereby interfering with the malignant behavior of HCC cells. In conclusion, ASMTL-AS1 acts as a carcinogen in HCC through competing endogenous RNA (ceRNA) activity in the miR-1343-3p/LAMC1 axis. Our findings demonstrate that regulating ASMTL-AS1/miR-1343-3p/LAMC1-mediated HCC cell malignancy might be an effective method to interfere with HCC progression.
长链非编码 RNA（lncRNA）是肝细胞癌（HCC）发生和发展的关键调控因子。我们旨在鉴定 lncRNA ASMTL-AS1 在 HCC 恶性肿瘤中的功能。评估了 HCC 组织和细胞中 ASMTL-AS1、miR-1343-3p 和 LAMC1（层粘连蛋白亚单位γ1）的表达。通过细胞计数试剂盒-8（CCK8）和 Transwell 迁移实验来确定 ASMTL-AS1 对 HCC 细胞增殖和迁移的影响。通过 Western blot 检测 Bax 和 Bcl-2 蛋白表达来鉴定细胞凋亡，并用异种移植实验来研究肿瘤生长。通过荧光素酶报告和 RNA 免疫沉淀实验验证了 miR-1343-3p 与 ASMTL-AS1 或 LAMC1 之间的相互作用。ASMTL-AS1 和 LAMC1 在 HCC 组织和细胞中高表达，而 miR-1343-3p 表达水平较低。临床研究表明，HCC 组织中 miR-1343-3p 的表达与 ASMTL-AS1 或 LAMC1 的表达呈负相关。功能实验表明，ASMTL-AS1 沉默抑制 HCC 细胞增殖和迁移，增加细胞凋亡。更有趣的是，ASMTL-AS1 作为 ceRNA 可以吸附 miR-1343-3p，miR-1343-3p 靶向 LAMC1 的 3'-UTR，从而干扰 HCC 细胞的恶性行为。总之，ASMTL-AS1 通过在 miR-1343-3p/LAMC1 轴上的竞争性内源 RNA（ceRNA）活性在 HCC 中发挥致癌作用。我们的研究结果表明，调节 ASMTL-AS1/miR-1343-3p/LAMC1 介导的 HCC 细胞恶性可能是干扰 HCC 进展的有效方法。
