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长链非编码RNA SPRY4‑IT1在体外缺氧条件下上调并促进前列腺癌细胞增殖。

LncRNA SPRY4‑IT1 is upregulated and promotes the proliferation of prostate cancer cells under hypoxia in vitro.

作者信息

Sang Weicong, Zhu Rujian, Liu Dong, Gong Min

机构信息

Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.

出版信息

Oncol Lett. 2023 Feb 17;25(4):138. doi: 10.3892/ol.2023.13724. eCollection 2023 Apr.

Abstract

The incidence and mortality rate of prostate cancer are among the highest for all cancers worldwide; this disease has a high cancer mortality rate in males, following lung cancer. Sprouty4-intron 1 (SPRY4-IT1) has been shown to play a variety of roles in tumors. Our previous study demonstrated that SPRY4-IT1 sponges microRNA-101-3p to promote the proliferation and metastasis of bladder cancer cells by upregulating enhancer of zeste homolog 2 expression; however, the role of SPRY4-IT1 in prostate cancer has not been fully established. In the present study, the expression levels, effects and mechanism of action of SPRY4-IT1 were investigated in prostate cancer tissues and cell lines using reverse transcription-quantitative PCR, western blotting, Cell Counting Kit-8 and flow cytometry assays. The results indicated that SPRY4-IT1 expression was upregulated in prostate cancer tissues and cell lines. Furthermore, hypoxia increased the expression levels of SPRY4-IT1 in prostate cancer cells. Knockdown of SPRY4-IT1 expression led to S-phase arrest, decreased expression levels of the cell cycle-associated proteins CDK2 and cyclin D1. AKT phosphorylation was also reduced by SPRY4-IT1 knockdown. In summary, the findings indicate the elevation of SPRY4-IT1 expression in prostate cancer. Under hypoxic conditions , SPRY4-IT1 overexpression promoted prostate cancer cell proliferation via a mechanism involving regulation of the cell cycle and the PI3K/AKT signaling pathway. Therefore, it may provide a basis for the development of targeted therapies.

摘要

前列腺癌的发病率和死亡率在全球所有癌症中位居前列;在男性中,这种疾病的癌症死亡率很高,仅次于肺癌。Sprouty4内含子1(SPRY4-IT1)已被证明在肿瘤中发挥多种作用。我们之前的研究表明,SPRY4-IT1通过上调zeste同源物2增强子的表达来海绵化微小RNA-101-3p,从而促进膀胱癌细胞的增殖和转移;然而,SPRY4-IT1在前列腺癌中的作用尚未完全明确。在本研究中,使用逆转录定量PCR、蛋白质印迹、细胞计数试剂盒8和流式细胞术检测,对前列腺癌组织和细胞系中SPRY4-IT1的表达水平、作用及其作用机制进行了研究。结果表明,SPRY4-IT1在前列腺癌组织和细胞系中的表达上调。此外,缺氧增加了前列腺癌细胞中SPRY4-IT1的表达水平。敲低SPRY4-IT1的表达导致S期停滞,细胞周期相关蛋白CDK2和细胞周期蛋白D1的表达水平降低。敲低SPRY4-IT1也降低了AKT磷酸化水平。总之,这些发现表明前列腺癌中SPRY4-IT1表达升高。在缺氧条件下,SPRY4-IT1的过表达通过涉及调节细胞周期和PI3K/AKT信号通路的机制促进前列腺癌细胞增殖。因此,这可能为开发靶向治疗提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6bf/9996607/e6857060af30/ol-25-04-13724-g00.jpg

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