LOC100996425 通过介导肝细胞核因子 4A 和 AMPK/mTOR 通路在前列腺癌中发挥作用。
LOC100996425 acts as a promoter in prostate cancer by mediating hepatocyte nuclear factor 4A and the AMPK/mTOR pathway.
机构信息
Department of Urology, The Second Hospital of Jilin University, Changchun, China.
Department of Neurosurgery, The Second Hospital of Jilin University, Changchun, China.
出版信息
J Cell Mol Med. 2021 Sep;25(17):8174-8186. doi: 10.1111/jcmm.16657. Epub 2021 Jul 26.
The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Then, the target gene of LOC100996425 was determined with lncRNA target prediction website and further verification was obtained through luciferase assay and ribonucleoprotein immunoprecipitation. After that, PCa cells were introduced with LOC100996425, HNF4A, siLOC100996425 or siHNF4A to explore the specific significance of LOC100996425 and HNF4A in PCa. The mechanism associated with AMPK/mTOR pathway was investigated using AMPK inhibitor or activator. LOC100996425 was up-regulated, while HNF4A was down-regulated in the PCa tissues. HNF4A was a target gene of LOC100996425. PCa cells transfected with either siLOC100996425 or HNF4A displayed reduced rates of PCa cell proliferation and migration while elevating cell apoptosis. HNF4A overexpression reversed the promotive effect of LOC100996425 overexpression on PCa. The activation of AMPK pathway involved in the cancer progression mediated by LOC100996425. Down-regulation of LOC100996425 retards progression of PCa through HNF4A-mediated AMPK/mTOR pathway.
长链非编码 RNA（lncRNA）、差异表达基因和信号在前列腺癌（PCa）中的作用一直是研究的主题。本研究通过 AMPK/mTOR 通路靶向肝细胞核因子 4A（HNF4A），确定了 LOC100996425 对人前列腺癌细胞的影响。获得 PCa 和相邻正常组织，以表征 LOC100996425、HNF4A 和 AMPK/mTOR 通路相关基因的表达模式。然后，使用 lncRNA 靶标预测网站确定 LOC100996425 的靶基因，并通过荧光素酶测定和核糖核蛋白免疫沉淀进一步验证。之后，将 LOC100996425、HNF4A、siLOC100996425 或 siHNF4A 引入 PCa 细胞，以探讨 LOC100996425 和 HNF4A 在 PCa 中的特定意义。使用 AMPK 抑制剂或激活剂研究与 AMPK/mTOR 通路相关的机制。LOC100996425 在 PCa 组织中上调，而 HNF4A 下调。HNF4A 是 LOC100996425 的靶基因。转染 siLOC100996425 或 HNF4A 的 PCa 细胞显示出较低的 PCa 细胞增殖和迁移率，同时提高了细胞凋亡率。HNF4A 过表达逆转了 LOC100996425 过表达对 PCa 的促进作用。LOC100996425 介导的癌症进展中 AMPK 通路的激活。下调 LOC100996425 通过 HNF4A 介导的 AMPK/mTOR 通路减缓 PCa 的进展。
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