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miR-122-5p 通过抑制 DUSP4 表达抑制 PTC 的致癌作用。

miR‑122‑5p suppresses the oncogenesis of PTC by inhibiting DUSP4 expression.

机构信息

Department IV of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050005, P.R. China.

Department II of Oncology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050005, P.R. China.

出版信息

Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.12007. Epub 2021 Mar 24.

Abstract

MicroRNAs (miRNAs or miRs) play an important role in regulating the occurrence and development of papillary thyroid carcinoma (PTC). miR‑122‑5p is widely considered a tumour inhibitor, which has not been fully explored in PTC. Bioinformatics analysis identified dual specificity phosphatase 4 (DUSP4), a tumour promoter gene for PTC, as a downstream target of miR‑122‑5p. The aim of the present study was to investigate the role and molecular mechanism of miR‑122‑5p in PTC oncogenesis. In this study, the expression pattern of miR‑122‑5p in PTC cancer tissues and PTC cell lines was investigated via reverse transcription‑quantitative PCR. Furthermore, the roles of miR‑122‑5p in PTC were explored using gain‑of‑function and loss‑of‑function assays. The results revealed that the expression of miR‑122‑5p was significantly lower in PTC cancer tissues, especially in cancer tissues with significant invasion or metastasis. Overexpression of miR‑122‑5p caused by miR‑122‑5p mimics inhibited the proliferation, invasion, and migration of the PTC cell line K1, while knockdown of miR‑122‑5p by miR‑122‑5p inhibitors exhibited the opposite effect. Furthermore, assays revealed that miR‑122‑5p overexpression inhibited tumour growth. In addition, miR‑122‑5p was negatively correlated with DUSP4 expression in PTC cancer tissues. miR‑122‑5p overexpression inhibited DUSP4 expression in K1 cells, while miR‑122‑5p downregulation produced the inverse effect. Specifically, a luciferase reporter assay confirmed the binding sites of miR‑122‑5p on the 3'‑UTR of DUSP4, demonstrating the targeting effect of miR‑122‑5p on DUSP4. miR‑122‑5p inhibited the oncogenesis of PTC by targeting DUSP4, revealing the potential application value of miR‑122‑5p in the diagnosis and treatment of PTC.

摘要

微小 RNA(miRNAs 或 miRs)在调节甲状腺乳头状癌(PTC)的发生和发展中起着重要作用。miR-122-5p 被广泛认为是一种肿瘤抑制剂,但在 PTC 中尚未得到充分研究。生物信息学分析确定双特异性磷酸酶 4(DUSP4),一种 PTC 的肿瘤促进基因,是 miR-122-5p 的下游靶标。本研究旨在探讨 miR-122-5p 在 PTC 致癌中的作用和分子机制。在本研究中,通过逆转录-定量 PCR 研究了 miR-122-5p 在 PTC 癌组织和 PTC 细胞系中的表达模式。此外,通过功能获得和功能丧失实验探索了 miR-122-5p 在 PTC 中的作用。结果表明,miR-122-5p 在 PTC 癌组织中的表达明显降低,尤其是在侵袭或转移明显的癌组织中。miR-122-5p 模拟物引起的 miR-122-5p 过表达抑制 PTC 细胞系 K1 的增殖、侵袭和迁移,而 miR-122-5p 抑制剂对 miR-122-5p 的敲低则产生相反的效果。此外,体内实验表明 miR-122-5p 过表达抑制肿瘤生长。此外,miR-122-5p 在 PTC 癌组织中与 DUSP4 表达呈负相关。miR-122-5p 过表达抑制 K1 细胞中的 DUSP4 表达,而 miR-122-5p 下调则产生相反的效果。具体而言,荧光素酶报告基因实验证实了 miR-122-5p 与 DUSP4 3'UTR 的结合位点,证明了 miR-122-5p 对 DUSP4 的靶向作用。miR-122-5p 通过靶向 DUSP4 抑制 PTC 的癌发生,揭示了 miR-122-5p 在 PTC 诊断和治疗中的潜在应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a40e/7986011/4c470061b9d7/mmr-23-05-12007-g00.jpg

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