Sang Weicong, Zhu Rujian, Liu Dong, Gong Min
Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, P.R. China.
Oncol Lett. 2023 Feb 17;25(4):138. doi: 10.3892/ol.2023.13724. eCollection 2023 Apr.
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.
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。