Department of Internal Medicine Oncology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.
Department of the Radiotherapy, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.
Ann Clin Lab Sci. 2023 Jan;53(1):42-51.
Long noncoding RNAs (lncRNAs) are crucial regulators of lung adenocarcinoma (LUAD) progression. Herein, we explored the role of miR-490-3p and the underlying molecular mechanism involving key lncRNAs and pathways in LUAD.
Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression of lncRNA NEAT1 and miR-490-3p in LUAD cells and tissues. Western blotting was used to determine protein expression levels of the Ras homologous gene family member A/Rho-related protein kinase (RhoA/ROCK) signal pathway marker. Considering cell functions, Cell Counting Kit-8 (CCK-8), Transwell, and xenograft experiments were employed to evaluate LUAD cell proliferation, migration, and tumor growth, respectively. The relationship between miR-490-3p and lncRNA NEAT1 was analyzed using a luciferase reporter assay.
Herein, we found that miR-490-3p expression was significantly low in LUAD cells and tissues. MiR-490-3p overexpression markedly suppressed tumor growth, the RhoA/ROCK signaling pathway, migration, and proliferation of LUAD cells. Moreover, lncRNA NEAT1, which is highly expressed in LUAD, was detected upstream of miR-490-3p. Upregulation of lncRNA NEAT1 exacerbated the behavior of LUAD cells and offset the suppressive influence of miR-490-3p-mediated upregulation on malignant LUAD cell behavior.
MiR-490-3p sponging by lncRNA NEAT1 could hamper LUAD progression by inhibiting the RhoA/ROCK signaling pathway. These findings provide new insights for LUAD diagnosis and treatment.
长链非编码 RNA（lncRNA）是肺腺癌（LUAD）进展的关键调节因子。在此，我们探讨了 miR-490-3p 的作用及其在 LUAD 中涉及关键 lncRNA 和途径的潜在分子机制。
采用逆转录定量 PCR（RT-qPCR）检测 LUAD 细胞和组织中 lncRNA NEAT1 和 miR-490-3p 的表达。采用 Western blot 检测 Ras 同源基因家族成员 A/Rho 相关蛋白激酶（RhoA/ROCK）信号通路标记物的蛋白表达水平。考虑细胞功能，采用细胞计数试剂盒-8（CCK-8）、Transwell 和异种移植实验分别评估 LUAD 细胞增殖、迁移和肿瘤生长。采用荧光素酶报告基因检测分析 miR-490-3p 与 lncRNA NEAT1 的关系。
在此，我们发现 miR-490-3p 在 LUAD 细胞和组织中的表达显著降低。miR-490-3p 的过表达显著抑制了 LUAD 细胞的肿瘤生长、RhoA/ROCK 信号通路、迁移和增殖。此外，在 LUAD 中高表达的 lncRNA NEAT1 被检测到位于 miR-490-3p 的上游。上调 lncRNA NEAT1 加剧了 LUAD 细胞的行为，并抵消了 miR-490-3p 介导的上调对恶性 LUAD 细胞行为的抑制作用。
lncRNA NEAT1 对 miR-490-3p 的海绵作用可以通过抑制 RhoA/ROCK 信号通路来阻碍 LUAD 的进展。这些发现为 LUAD 的诊断和治疗提供了新的思路。
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