MicroRNA-508-3p 通过靶向 G1 到 S 期转变 1 (GSPT1) 蛋白调节人类肺癌细胞的增殖。

IF 1.4 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Acta biochimica Polonica Pub Date : 2023-11-22 DOI:10.18388/abp.2020_6660
Xingyou Chen, Chen Feng, Jiliang Zha, Zihao Shen, Wei Ji
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引用次数: 0

摘要

目的:由于其关键的癌症调控作用,microRNA-508-3p 已被报道为潜在的抗癌治疗分子靶点。方法:采用 qRT-PCR 技术估测组织样本中 microRNA-508-p 的相对基因表达量。用细胞计数试剂盒-8测定癌细胞的增殖情况。通过克隆形成试验分析癌细胞的集落形成。采用流式细胞技术了解有丝分裂期分布。Edu-Hoechst 染色法用于评估细胞活力。利用硅分析和双荧光素酶检测法确定了肺癌中 microRNA-508-3p 的靶点。免疫荧光和 Western 印迹研究用于检测蛋白质的相对表达。大鼠模型用于体内实验过程:研究结果表明,microRNA-508-3p 在肺癌中的表达明显下调。研究结果表明,microRNA-508-3p 在肺癌中的表达水平明显下调,而较低的表达水平与肺癌患者的生存率较低有关。研究发现,microRNA-508-3p 的过度表达会降低癌细胞的增殖和存活能力,并通过靶向 G1 到 S 期转变 1(GSPT1)蛋白诱导有丝分裂细胞周期停滞在 G1 阶段。MicroRNA-508-3p的上调抑制了大鼠模型体内肿瘤的生长:我们的研究发现,miR-508-3p 通过靶向 GSPT1 蛋白,是肺癌细胞增殖的关键调节因子。这凸显了 miR-508-3p 作为肿瘤抑制因子和肺癌治疗靶点的潜力。我们的发现为 miRNA 介导的癌症进展提供了机理上的见解,促使人们进一步研究这一错综复杂的调控网络。
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MicroRNA-508-3p regulates the proliferation of human lung cancer cells by targeting G1 to S phase transition 1 (GSPT1) protein.

Purpose: Due to its crucial cancer regulatory role, microRNA-508-3p has been reported as a potential therapeutic anticancer molecular target. The present work encompassed the molecular characterization of microRNA-508-3p in lung cancer emphasizing on understanding the possible mechanism of its regulatory action.

Methods: qRT-PCR was performed to estimate the relative gene expression of microRNA-508-p in the tissue samples. The proliferation of cancer cells was determined by cell counting kit-8. The colony formation from cancer cells was analyzed by clonogenic assay. Mitotic phase distribution was understood by employing the flow cytometric technique. Edu-Hoechst staining was used for the assessment of cell viability. In silico analysis and dual-luciferase assay were used for target identification of microRNA-508-3p in lung cancer. Immunofluorescence and western blotting studies were carried out for relative protein expression. The rat models were used for performing the in vivo experimental procedures.

Results: The study showed the significant down-regulation of microRNA-508-3p in lung cancer. The lower expression levels of microRNA-508-3p were shown to be associated with poor survival of lung cancer patients. The over-expression of microRNA-508-3p was found to decline the proliferation and viability of cancer cells together with the induction of mitotic cell cycle arrest at G1 by targeting G1 to S phase transition 1 (GSPT1) protein. MicroRNA-508-3p up-regulation inhibited the in vivo tumor growth in rat models.

Conclusion: Our study identifies miR-508-3p as a pivotal regulator of lung cancer cell proliferation by targeting the GSPT1 protein. This highlights its potential as a tumor suppressor and a therapeutic target for lung cancer. Our findings offer mechanistic insights into miRNA-mediated cancer progression, prompting further research in this intricate regulatory network.

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来源期刊
Acta biochimica Polonica
Acta biochimica Polonica 生物-生化与分子生物学
CiteScore
2.40
自引率
0.00%
发文量
99
审稿时长
4-8 weeks
期刊介绍: Acta Biochimica Polonica is a journal covering enzymology and metabolism, membranes and bioenergetics, gene structure and expression, protein, nucleic acid and carbohydrate structure and metabolism.
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