Precision Medical Center, Affiliated Hospital of Beihua University, Jilin, Jilin 132011, P.R. China.
Department of Thoracic Surgery, Jilin City Central Hospital, Capital Medical University, Jilin, Jilin 132010, P.R. China.
Oncol Rep. 2020 Oct;44(4):1550-1560. doi: 10.3892/or.2020.7693. Epub 2020 Jul 15.
PSMA3 antisense RNA 1 (PSMA3‑AS1), a long noncoding RNA, promotes the progression of esophageal squamous cell carcinoma. However, no study to date has explored the expression or roles of PSMA3‑AS1 in non‑small cell lung carcinoma (NSCLC). The present study examined the expression profile and role of PSMA3‑AS1 in NSCLC. It also aimed to identify how PSMA3‑AS1 promotes the malignant phenotype of NSCLC cells. PSMA3‑AS1 expression in NSCLC tissues and cell lines was measured by reverse transcription‑quantitative polymerase chain reaction. Cell Counting Kit‑8, cell apoptosis, Transwell migration and invasion, and xenograft tumor assays were conducted to study the effects of PSMA3‑AS1 on the aggressive phenotype of NSCLC cells. Furthermore, bioinformatics analysis, RNA immunoprecipitation, luciferase reporter assay, western blotting, and rescue experiments were used to elucidate the interaction among PSMA3‑AS1, microRNA‑409‑3p (miR‑409‑3p), and spindlin 1 (SPIN1) in NSCLC cells. In the present study, high levels of PSMA3‑AS1 were confirmed in both NSCLC tissues and cell lines. An increased PSMA3‑AS1 level was correlated with advanced tumor‑node‑metastasis stage and increased lymph node metastasis. Patients with NSCLC with high PSMA3‑AS1 levels had shorter overall survival than those with low PSMA3‑AS1 levels. PSMA3‑AS1 depletion significantly decreased NSCLC cell proliferation, migration, and invasion, as well as substantially increased cell apoptosis in vitro. Furthermore, PSMA3‑AS1 deficiency decreased NSCLC tumor growth in vivo. Through molecular mechanism assays, it was revealed that PSMA3‑AS1 acted as a molecular sponge for miR‑409‑3p and consequently increased SPIN1 expression. Notably, rescue experiments revealed that the inhibition of miR‑409‑3p or restoration of SPIN1 expression abrogated the effects of PSMA3‑AS1 knockdown in NSCLC cells. Collectively, PSMA3‑AS1 functioned as an oncogenic long noncoding RNA in NSCLC. PSMA3‑AS1 sponged miR‑409‑3p and thus increased SPIN1 expression, promoting the aggressive phenotype of NSCLC cells.
PSMA3 反义 RNA 1（PSMA3-AS1）是一种长链非编码 RNA，可促进食管鳞状细胞癌的进展。然而，迄今为止尚无研究探讨 PSMA3-AS1 在非小细胞肺癌（NSCLC）中的表达或作用。本研究检测了 PSMA3-AS1 在 NSCLC 中的表达谱和作用，并旨在确定 PSMA3-AS1 如何促进 NSCLC 细胞的恶性表型。通过逆转录-定量聚合酶链反应检测 NSCLC 组织和细胞系中的 PSMA3-AS1 表达。通过细胞计数试剂盒-8、细胞凋亡、Transwell 迁移和侵袭以及异种移植肿瘤实验研究 PSMA3-AS1 对 NSCLC 细胞侵袭表型的影响。此外，还进行了生物信息学分析、RNA 免疫沉淀、荧光素酶报告基因检测、Western blot 分析和挽救实验，以阐明 NSCLC 细胞中 PSMA3-AS1、微小 RNA-409-3p（miR-409-3p）和纺锤体 1（SPIN1）之间的相互作用。本研究证实，PSMA3-AS1 在 NSCLC 组织和细胞系中均呈高表达。PSMA3-AS1 水平升高与肿瘤-淋巴结-转移分期较晚和淋巴结转移增加相关。PSMA3-AS1 水平较高的 NSCLC 患者总生存期短于 PSMA3-AS1 水平较低的患者。PSMA3-AS1 耗竭显著降低 NSCLC 细胞的增殖、迁移和侵袭能力，显著增加体外细胞凋亡。此外，PSMA3-AS1 缺失可减少 NSCLC 肿瘤在体内的生长。通过分子机制检测发现，PSMA3-AS1 作为 miR-409-3p 的分子海绵，进而增加 SPIN1 表达。值得注意的是，挽救实验显示，抑制 miR-409-3p 或恢复 SPIN1 表达可消除 PSMA3-AS1 敲低对 NSCLC 细胞的影响。总之，PSMA3-AS1 在 NSCLC 中作为一种致癌的长链非编码 RNA 发挥作用。PSMA3-AS1 海绵吸附 miR-409-3p，从而增加 SPIN1 表达，促进 NSCLC 细胞的侵袭表型。
