التفاصيل البيبلوغرافية
| العنوان: |
Circ-CL5A1 受 TDP-43 调控并抑制肝细胞癌转移的研究. |
| العنوان البديل: |
Circ-COL5A1 is Regulated by TDP-43 and Inhibit HCC Metastasis. |
| المؤلفون: |
王 硕1 docwang13166003267@163.com, 孔睿佼2, 井 杰1, 刘海东1, 贾 音1, 刘善荣1 lssbiomed@163.com |
| المصدر: |
Progress in Modern Biomedicine. 6/15/2020, Vol. 20 Issue 12, p2036-2041. 6p. |
| مصطلحات موضوعية: |
*RNA interference, *CANCER stem cells, *RNA-binding proteins, *GENE expression, *PROTEIN expression |
| الملخص (بالإنجليزية): |
Objective: To explore the biological function, mechanism and regulation factor of circ-COL5A1, providing candidate molecules for the intervention and further understanding of HCC metastasis. Methods: The target molecule Circ-COL5A1 were selected based on the preliminary work. The biological function of circ-COL5A1 is verified through transwell assay and wound healing assay. Bioinformatic analysis, gene expression interference and RNA immunoprecipitation (RIP) experiments were employed to explore the regulation mechanism of circ-COL5A1. Western blot and quantitative real-time PCR (qRT-PCR) were employed to explore the down stream pathway of circ-COL5A1. Results: The expression of Circ-COL5A1 is down-regulated in HCC cancer stem cells. And Circ-COL5A1 overexpressed inhibit the invasion and migration ability in Huh 7 and HCC-LM3 cell lines. The result of RIP experiments showed that RNA-binding protein (RBP)TDP-43 can enrich the linear precursor and dissociate after the formation of the circular structure. Circ-COL5A1 can also reduce the protein expression of its maternal gene COL51, which may affect multiple signaling pathways and thus interfere with the metastasis process of HCC. Conclusion: Endogenous Circ-COL5A1 can inhibit the metastasis ability of HCC cell lines, and may provide candidate molecules for blocking HCC metastasis. TDP-43 promotes the biogenesis of Circ-COL5A1, suggesting that RBPs are important regulators in the process of circRNA biogenesis. Circ-COL5A1 inhibits protein expression of its maternal genes COL5A1 through post-transcription regulation. [ABSTRACT FROM AUTHOR] |
| Abstract (Chinese): |
目的：探索 Circ-COL5A1 的生物学功能、调控机制和作用机制，进而为 HCC 转移的干预提供候选分子并进一步了解 HCC 转移。方法：通过前期工作基础选定目标分子 Circ-COL5A1。通过慢病毒转染在 HCC 细胞系中过表达 Circ-COL5A1，进而通过划 痕愈合实验、transwell 实验观察 Circ-COL5A1 的生物学功能。通过生物信息学分析、表 达 干扰实验和 RNA 免疫共沉淀（RIP）实验 探究目标分子的调控机制。通过 western blot 技术、实时定量 PCR (qRT-PCR) 技术对目标分子的下游作用机制进行初步探索。结 果：Circ-COL5A1 在肝癌干细胞中表达下调，而且 Circ-COL5A1 过表达的 HCC 细胞系侵袭和迁移能力减弱。在 Circ-COL5A1 生 物学合成过程中，RNA 结合蛋白 TDP-43 可以富集其线性前体，并 在 环 化 结 构 形成后解离。Circ-COL5A1 还可以降低其亲本基因 V 型胶原蛋白琢 1 链 (COL5A1) 的蛋白质表达水平，这可能会影响多个信号通路进而干预 HCC 的转移过程。结论：内源性的 Circ-COL5A1 可以抑制 HCC 的转移能力，可以为阻断 HCC 转移提供候选分子。TDP-43 的促进环状 RNA 形成提示 RNA 结合蛋 白是环状 RNA 生物学合成过程中的重要调控因子。Circ-COL5A1 可以通过转录后调控抑制其亲本基因 COL5A1 的表达。 [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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