Long Non-coding RNAs LINC01679 as a Competitive Endogenous RNAs Inhibits the Development and Progression of Prostate Cancer via Regulating the miR-3150a-3p/SLC17A9 Axis.
Long Non-coding RNAs LINC01679 as a Competitive Endogenous RNAs Inhibits the Development and Progression of Prostate Cancer via Regulating the miR-3150a-3p/SLC17A9 Axis.
复制标题
长非编码 RNA LINC01679 作为竞争性内源 RNA 通过调节 miR-3150a-3p/SLC17A9 轴抑制前列腺癌的发生和进展
DOI：
10.3389/fcell.2021.737812
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Zhu LJ
中科院分区：
文献类型：
--
作者：
Mi YY;Sun CY;Zhang LF;Wang J;Shao HB;Qin F;Xia GW;Zhu LJ
长非编码RNA（lncRNA）已被认为是预测癌症预后的候选因素。然而，lncRNA组合是否可用于预测前列腺癌（PCa）的总生存期（OS）仍不清楚。目前的工作重点是为PCa选择有效的OS相关lncRNA特征并研究其分子机制以提高预后预测的准确性。通过R软件“edgeR”包基于TCGA数据库获得差异表达lncRNA（DElncRNA）或差异表达基因（DEG）。通过单变量和多变量Cox回归筛选与PCa显着相关的lncRNA或mRNA，用于构建预后预测的风险模型。此外，该构建的风险模型通过 ROC 分析、单变量回归和 Kaplan-Meier (KM) 分析进行了验证。此外，我们通过生物信息学分析构建了lncRNA-miRNA-mRNA ceRNA网络。基于经过靶向 LINC01679/SLC17A9 的小干扰 RNA (siRNA) 和表达 LINC01679/SLC17A9 的载体转染的 PCa 细胞，进行集落形成、CCK-8、流式细胞术、划痕和 Transwell 测定。此后，通过 qRT-PCR、蛋白质印迹 (WB)、RNA Pull-down 和荧光素酶报告基因测定阐明了 ceRNA 机制。建立裸鼠肿瘤异种移植物以检查 LINC01679 在 PCa 细胞内的致癌性。根据我们的结果，LINC01679 耗尽在体内和体外促进细胞增殖、转移、肿瘤生长并抑制细胞凋亡，这也与较差的存活率相关。 LINC01679 通过海绵作用来调节 miR-3150a-3p 水平。重要的是，miR-3150a-3p 过表达与 PCa 细胞增殖增加和凋亡减少有关。拯救实验表明，miR-3150a-3p 模拟物拯救了 LINC01679 上调介导的 PCa 进展抑制，但 SLC17A9 下调逆转了 miR-3150a-3p 抑制剂介导的 PCa 进展抑制。重要的是，SLC17A9 下调挽救了 LINC01679 上调介导的对 PCa 进展的抑制。 LINC01679 和 SLC17A9 与 PCa 的某些临床病理特征及其预后结果密切相关。此外，LINC01679 是通过调节 miR-3150a-3p/SLC17A9 轴抑制 PCa 发育的 ceRNA。
Long non-coding RNAs (lncRNAs) have been indicated as the candidate factors to predict cancer prognosis. However, it is still unknown whether lncRNA combinations may be utilized for predicting overall survival (OS) of prostate cancer (PCa). The present work focused on selecting the potent OS-related lncRNA signature for PCa and studying its molecular mechanism to enhance the prognosis prediction accuracy. Differentially expressed lncRNAs (DElncRNAs) or differentially expressed genes (DEGs) were obtained based on TCGA database by R software “edgeR” package. lncRNAs or mRNAs significantly related to PCa were screened through univariate as well as multivariate Cox regression, for the construction of the risk model for prognosis prediction. Moreover, this constructed risk model was validated through ROC analysis, univariate regression, and Kaplan–Meier (KM) analysis. Additionally, we built a lncRNA–miRNA–mRNA ceRNA network through bioinformatics analysis. Colony formation, CCK-8, flow cytometry, scratch, and Transwell assays were performed based on PCa cells subjected to small interfering RNA (siRNA) targeting LINC01679/SLC17A9 and vector expressing LINC01679/SLC17A9 transfection. Thereafter, the ceRNA mechanism was clarified via qRT-PCR, Western blotting (WB), RNA pull-down, and luciferase reporter assays. Nude mouse tumor xenograft was established to examine LINC01679’s oncogenicity within PCa cells. According to our results, LINC01679 depletion promoted cell proliferation, metastasis, tumor growth, and inhibited cell apoptosis in vivo and in vitro, which was also associated with poor survival. LINC01679 regulated miR-3150a-3p level by sponging it. Importantly, miR-3150a-3p overexpression was related to the increased proliferation and decreased apoptosis of PCa cells. Rescue assays suggested that miR-3150a-3p mimics rescued the repression on PCa progression mediated by LINC01679 upregulation, but SLC17A9 downregulation reversed the miR-3150a-3p inhibitor-mediated repression on PC progression. Importantly, SLC17A9 downregulation rescued the repression on PCa progression mediated by LINC01679 upregulation. LINC01679 and SLC17A9 are tightly associated with certain clinicopathological characteristics of PCa and its prognostic outcome. In addition, LINC01679 is the ceRNA that suppresses PCa development through modulating the miR-3150a-3p/SLC17A9 axis.
登录
查看更多内容
鉴定有助于 HBV 相关 HCC 发病机制的潜在 miRNA-mRNA 调控网络
影响因子：
7.4
作者：
Lou, Weiyang;Liu, Jingxing;Fan, Weimin
通讯作者：
Fan, Weimin
影响因子：
3.5
作者：
Zhang, Yuelong;Zhang, Dahong;Zhang, Qi
通讯作者：
Zhang, Qi
LncRNA FOXD2-AS1 作为竞争性内源 RNA 通过海绵 miR-7-5p 在甲状腺癌中调节 TERT 表达
影响因子：
5.2
作者：
Liu, Xiaoli;Fu, Qingfeng;Sun, Hui
通讯作者：
Sun, Hui
影响因子：
5.3
作者：
Wu, Meng;Huang, Yawei;Xi, Xiaoqing
通讯作者：
Xi, Xiaoqing
影响因子：
5.2
作者：
Lingadahalli, Shreyas;Jadhao, Sudhir;Cheung, Edwin
通讯作者：
Cheung, Edwin