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LncRNA PSMA3-AS1 promotes cell proliferation, migration, and invasion in ovarian cancer by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis
Environmental Toxicology ( IF 4.5 ) Pub Date : 2021-09-14 , DOI: 10.1002/tox.23370
Zhihong Xu 1 , Hui Jin 1 , Xiaoyang Duan 1 , Hong Liu 2 , Xiwa Zhao 2 , Shaoshuang Fan 1 , Yan Wang 3 , Tiezhu Yao 4
Affiliation  

The crucial roles of the long noncoding RNAs (lncRNAs) in the development of ovarian cancer (OC) have been extensively studied. According to the prediction result from the Kaplan–Meier Plotter database, high expression of lncRNA proteasome subunit α type-3 antisense RNA1 (PSMA3-AS1) is associated with the poor prognosis in patients with OC. Thus, the study aimed to investigate the role of lncRNA PSMA3-AS1 in OC. Reverse transcription quantitative polymerase chain reaction analysis revealed that PSMA3-AS1 expression was significantly upregulated in OC cells and tissues. PSMA3-AS1 silencing inhibited OC cell proliferation, migration, and invasion, as shown by results of cell counting kit-8, colony formation, wound healing, and Transwell assays, respectively. Additionally, PSMA3-AS1 deficiency suppressed tumor growth in vivo. Mechanistically, luciferase reporter and RNA pulldown assays implied that PSMA3-AS1 served as a competing endogenous RNA for miR-378a-3p to upregulate the expression of polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). GALNT3 was a target gene of miR-378a-3p in OC. Moreover, PSMA3-AS1 activated the PI3K/Akt pathway by upregulating GALNT3 expression. Overall, PSMA3-AS1 promotes OC cell proliferation, migration, invasion, and xenograft tumor growth by activating the PI3K/Akt pathway via the miR-378a-3p/GALNT3 axis.

中文翻译:

LncRNA PSMA3-AS1 通过 miR-378a-3p/GALNT3 轴激活 PI3K/Akt 通路促进卵巢癌的细胞增殖、迁移和侵袭

长链非编码 RNA (lncRNA) 在卵巢癌 (OC) 发展中的关键作用已被广泛研究。根据 Kaplan-Meier Plotter 数据库的预测结果,lncRNA 蛋白酶体亚基 α 3 型反义 RNA1(PSMA3-AS1)的高表达与 OC 患者的不良预后相关。因此,本研究旨在探讨 lncRNA PSMA3-AS1 在 OC 中的作用。逆转录定量聚合酶链反应分析显示,PSMA3-AS1 在 OC 细胞和组织中的表达显着上调。PSMA3-AS1 沉默抑制 OC 细胞增殖、迁移和侵袭,分别由细胞计数 kit-8、集落形成、伤口愈合和 Transwell 测定的结果显示。此外,PSMA3-AS1 缺乏抑制了体内肿瘤的生长。机械地,荧光素酶报告基因和 RNA pulldown 分析表明 PSMA3-AS1 作为 miR-378a-3p 的竞争性内源性 RNA 可上调多肽 N-乙酰半乳糖胺基转移酶 3 (GALNT3) 的表达。GALNT3 是 OC 中 miR-378a-3p 的靶基因。此外,PSMA3-AS1 通过上调 GALNT3 表达激活 PI3K/Akt 通路。总体而言,PSMA3-AS1 通过 miR-378a-3p/GALNT3 轴激活 PI3K/Akt 通路来促进 OC 细胞增殖、迁移、侵袭和异种移植肿瘤生长。
更新日期:2021-11-03
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