Department of Respiratory Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 571100, P.R. China.
Department of Anesthesia, Hainan General Hospital, Haikou, Hainan 570311, P.R. China.
Int J Mol Med. 2021 Feb;47(2):659-667. doi: 10.3892/ijmm.2020.4826. Epub 2020 Dec 22.
Increasing evidence has demonstrated the important roles of long non‑coding (lnc) RNA in non‑small cell lung cancer (NSCLC). lncRNA gastric cancer‑associated transcript 1 (GACAT1) has been reported to play an oncogenic role in different types of cancer; however, the function of GACAT1 in NSCLC remains unclear. The present study found that GACAT1 was overexpressed in NSCLC tissues and was associated with poor outcomes in patients with NSCLC. Functional experiments revealed that GACAT1 downregulation inhibited proliferation, induced apoptosis and cell cycle arrest of 2 NSCLC cell lines. GACAT1 was found to target microRNA(miR)‑422a mechanically and negatively regulated miR‑422a expression. Reduced expression of miR‑422a in NSCLC tissues was inversely correlated with that of GACAT1. Furthermore, YY1 transcription factor (YY1) was identified as a downstream miR‑422a target. Reduced expression of GACAT1 inactivated YY1 by sponging miR‑422a in NSCLC cells. YY1 reintroduction reversed the reduced proliferation of NSCLC cells via GACAT1 knockdown. Taken together, these results revealed the novel role of the GACAT1/miR‑422a pathway in the progression of NSCLC cell lines, providing a possible therapeutic strategy for NSCLC treatment.
越来越多的证据表明,长链非编码(lnc)RNA 在非小细胞肺癌(NSCLC)中具有重要作用。lncRNA 胃癌相关转录物 1(GACAT1)已被报道在不同类型的癌症中发挥致癌作用;然而,GACAT1 在 NSCLC 中的功能仍不清楚。本研究发现,GACAT1 在 NSCLC 组织中过表达,并与 NSCLC 患者的不良预后相关。功能实验表明,GACAT1 的下调抑制了 2 种 NSCLC 细胞系的增殖,诱导了细胞凋亡和细胞周期停滞。发现 GACAT1 通过机械靶向 microRNA(miR)-422a 并负调控 miR-422a 的表达。NSCLC 组织中 miR-422a 的表达降低与 GACAT1 的表达降低呈负相关。此外,YY1 转录因子(YY1)被鉴定为 miR-422a 的下游靶标。YY1 在 NSCLC 细胞中通过海绵吸附 miR-422a 使 GACAT1 表达降低失活。YY1 的重新引入通过 GACAT1 敲低逆转了 NSCLC 细胞增殖的减少。综上所述,这些结果揭示了 GACAT1/miR-422a 通路在 NSCLC 细胞系进展中的新作用,为 NSCLC 的治疗提供了一种可能的治疗策略。