Neuropilin-2 Inhibits Drug Resistance and Progression of Melanoma Involving the MiR-331-3p Regulated Cascade.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467216666221220111756

Qun Xie, Ruirui Zhang, Dandan Liu, Jing Yang, Qiang Hu, Chao Shan, Xiaohan Li

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Abstract

Background: MicroRNAs (miRs) are small noncoding RNAs that are crucial in the development and progression of tumours. Melanoma is an aggressive form of skin cancer and is resistant to most of the chemotherapeutic agents. However, the role of miRs in melanoma remains poorly studied.

Objective: The work aimed to demonstrate that miR-331-3p is downregulated in melanoma against the benign melanocytic nevi.

Methods: RT-PCR analysis was performed for the expression of proteins; cell proliferation and wound healing assays were carried out. Flow cytometry study was conducted for cell cycle analysis; colony formation assay was performed by soft agar method. For developing a tumour xenograft model, nu/nu mice were selected.

Results: Up-regulation of miR-331-3p in melanoma cells decreased cell proliferation, cell migration, and also drug resistance. Over-expression of miR-331-3p resulted in suppression of NRP2 and up-regulation of E-cadherin levels. Moreover, the levels of MDR1, ABCG-2, and ABCG-5 were decreased. However, the knockdown of NRP2 demonstrated similar effects as that of miR- 331-3p overexpression in tumour cells. Overexpression of miR-331-3p caused significant inhibition of tumour growth and its metastasis in mice model of melanoma, which was associated with depletion of NRP2 protein and increased expression of E-cadherin. However, the effects of miR- 331-3p on the migration, cell proliferation, and self-renewal were overturned by the upregulation of NRP2, which also resulted in the inhibition of E-cadherin and overexpression of MDR-1, ABCG-2, and ABCG-5.

Conclusion: The findings point out the key role of miR-331-3p in the progression and drug resistance of melanoma involving NRP2.

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Neuropilin-2通过MiR-331-3p调控级联抑制黑色素瘤的耐药和进展

背景:MicroRNAs (miRs)是一种小的非编码rna，在肿瘤的发生和发展中起着至关重要的作用。黑色素瘤是一种侵袭性皮肤癌，对大多数化疗药物都有抗药性。然而，miRs在黑色素瘤中的作用研究仍然很少。目的:本研究旨在证明miR-331-3p在黑色素瘤中对良性黑素细胞痣的下调。方法:采用RT-PCR分析蛋白表达;进行细胞增殖和伤口愈合试验。流式细胞术分析细胞周期;采用软琼脂法进行菌落形成试验。为了建立肿瘤异种移植模型，选择nu/nu小鼠。结果:在黑色素瘤细胞中上调miR-331-3p可降低细胞增殖、细胞迁移和耐药。过表达miR-331-3p导致NRP2被抑制，E-cadherin水平上调。MDR1、ABCG-2、ABCG-5水平降低。然而，在肿瘤细胞中，NRP2的下调表现出与miR- 331-3p过表达相似的效果。过表达miR-331-3p可显著抑制黑色素瘤小鼠模型的肿瘤生长及其转移，这与NRP2蛋白的缺失和E-cadherin的表达增加有关。然而，miR- 331-3p对迁移、细胞增殖和自我更新的影响被NRP2上调推翻，这也导致E-cadherin受到抑制，MDR-1、ABCG-2和ABCG-5过表达。结论:研究结果指出miR-331-3p在涉及NRP2的黑色素瘤的进展和耐药中起关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.