Zeng Qingqi, Liu Jia, Wu Qijin, Song Ruiyu, Miao Wen, Ma Yuting, Yang Hongbao
Department of Pharmacy, Jiangsu Health Vocational College, Nanjing, China.
Center for New Drug Safety Evaluation and Research, Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, China.
Cancer Biother Radiopharm. 2024 May;39(4):291-305. doi: 10.1089/cbr.2022.0031. Epub 2022 Sep 9.
Prostate cancer is a common male malignancy and the leading cause of cancer death in men. Long non-coding RNAs (lncRNAs), microRNA (miRNAs) and mRNAs networks mediate prostate cancer progression. Herein, we investigated the functions of lncRNA AC008972.1 and its regulatory mechanism in prostate cancer. The expression levels of lncRNA AC008972.1, miR-143-3p, and were detected in prostate cancer tissues and cell lines by reverse transcription-quantitative polymerase chain reaction. PC3 and LNCaP cells were used to establish lncRNA AC008972.1-knockdown, miR-143-3p-overexpressing, and thousand-and-one-amino acid 2 kinase ()-downregulated cells. Cell viability was examined by MTT assays and cell proliferation was detected by clone formation assay. Cell migration and invasion were detected by wound scratch assay and transwell chamber assay. The apoptosis rate was analyzed by flow cytometry. The protein expression was detected by Western blot assay. The RNA interaction was explored and validated by RNA binding protein immunoprecipitation (RIP) assay and dual luciferase activity assay. A mouse xenograft model was established to investigate the effect of lncRNA AC008972.1 on prostate cancer progression. High expression of lncRNA AC008972.1 was associated with low overall survival in prostate cancer patients. Downregulation of lncRNA AC008972.1 suppressed prostate cancer progression by inhibiting cell viability, proliferation, migration, and invasion, in addition to the EMT process, whereas cell apoptosis was significantly promoted. LncRNA AC008972.1 bound with miR-143-3p and negatively regulated miR-143-3p expression. MiR-143-3p overexpression suppressed prostate cancer malignant behaviors . expression was decreased by miR-143-3p through the complementary targeting of mRNA. Downregulation of lncRNA AC008972.1 mitigated prostate cancer malignant behaviors based on miR-143-3p/ node. Furthermore, the data of xenograft model experiment showed that inhibition of lncRNA AC008972.1 suppressed tumor growth . Knockdown of lncRNA AC008972.1 inhibits prostate cancer cell growth via downregulation of induced by miR-143-3p. LncRNA AC008972.1 acts as an oncogene in the progression of prostate cancer and may provide a novel therapeutic target for prostate cancer.
前列腺癌是一种常见的男性恶性肿瘤，也是男性癌症死亡的主要原因。长链非编码RNA（lncRNAs）、微小RNA（miRNAs）和信使RNA（mRNAs）网络介导前列腺癌的进展。在此，我们研究了lncRNA AC008972.1在前列腺癌中的功能及其调控机制。通过逆转录定量聚合酶链反应检测前列腺癌组织和细胞系中lncRNA AC008972.1、miR-143-3p的表达水平。使用PC3和LNCaP细胞建立lncRNA AC008972.1敲低、miR-143-3p过表达和1001个氨基酸2激酶（）下调的细胞。通过MTT法检测细胞活力，通过克隆形成试验检测细胞增殖。通过伤口划痕试验和Transwell小室试验检测细胞迁移和侵袭。通过流式细胞术分析细胞凋亡率。通过蛋白质免疫印迹法检测蛋白质表达。通过RNA结合蛋白免疫沉淀（RIP）试验和双荧光素酶活性试验探索并验证RNA相互作用。建立小鼠异种移植模型以研究lncRNA AC008972.1对前列腺癌进展的影响。lncRNA AC008972.1的高表达与前列腺癌患者的低总生存率相关。lncRNA AC008972.1的下调通过抑制细胞活力、增殖、迁移和侵袭以及上皮-间质转化（EMT）过程来抑制前列腺癌进展，同时显著促进细胞凋亡。lncRNA AC008972.1与miR-143-3p结合并负向调节miR-143-3p的表达。miR-143-3p过表达抑制前列腺癌的恶性行为。miR-143-3p通过对mRNA的互补靶向作用降低的表达。基于miR-143-3p/节点，lncRNA AC008972.1的下调减轻了前列腺癌的恶性行为。此外，异种移植模型实验数据表明，抑制lncRNA AC008972.1可抑制肿瘤生长。敲低lncRNA AC008972.1通过下调miR-143-3p诱导的来抑制前列腺癌细胞生长。lncRNA AC008972.1在前列腺癌进展中起癌基因作用，可能为前列腺癌提供新的治疗靶点。
