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miR-204-5p 抑制达卡巴嗪处理的黑色素瘤细胞中的细胞凋亡。

miR 204-5p inhibits apoptosis in dacarbazine-treated melanoma cells.

机构信息

Krasnoyarsk State Medical University, Krasnoyarsk, 660022, Russian Federation.

出版信息

Oncol Res. 2022 Nov 10;29(6):393-400. doi: 10.32604/or.2022.025816. eCollection 2021.

Abstract

Melanoma is one of the most aggressive types of malignant tumors, commonly affecting young individuals. The treatment of metastatic tumors remains obscure due to the resistance of tumor cells to drugs mediated by various mechanisms. The acquisition of a resistant phenotype is associated with both genetic and epigenetic alterations in cancer cells. Therefore, the current study aimed to investigate whether microRNA (miR)-204-5p could promote alterations in the cell cycle and apoptosis of dacarbazine (DTIC)-treated melanoma cells. Quantitative real time PCR showed that transfection of DTIC-treated SK-MEL-2 melanoma cells with miR-204-5p mimics significantly upregulated miR-204-5p. However, flow cytometric analysis revealed that the proportion of cells in different phases of the cell cycle remained unchanged. Additionally, the proportion of early apoptotic cells was notably enhanced following cell treatment with DTIC, accompanied by a profound increase in Ki-67 negative cells, as verified by an immunofluorescence assay. Furthermore, miR-204-5p overexpression reduced the percentage of early apoptotic DTIC-treated melanoma cells. The proportion of Ki-67 negative cells was only increased by 3%. Overall, the results of the current study indicated that miR-204-5p overexpression could mostly attenuate cell apoptosis in DTIC-treated cells rather than promote their transition from the G0 phase of the cell cycle in response to chemotherapeutic agent-induced stress.

摘要

黑色素瘤是最具侵袭性的恶性肿瘤之一,通常影响年轻人。由于肿瘤细胞对各种机制介导的药物的耐药性,转移性肿瘤的治疗仍然不清楚。耐药表型的获得与癌细胞的遗传和表观遗传改变有关。因此,本研究旨在探讨 microRNA (miR)-204-5p 是否可以促进达卡巴嗪 (DTIC) 处理的黑色素瘤细胞的细胞周期和细胞凋亡改变。实时定量 PCR 显示,miR-204-5p 模拟物转染 DTIC 处理的 SK-MEL-2 黑色素瘤细胞可显著上调 miR-204-5p。然而,流式细胞术分析显示,细胞周期不同阶段的细胞比例保持不变。此外,细胞用 DTIC 处理后,早期凋亡细胞的比例明显增加,Ki-67 阴性细胞显著增加,免疫荧光检测验证了这一点。此外,miR-204-5p 的过表达降低了早期凋亡的 DTIC 处理的黑色素瘤细胞的百分比。Ki-67 阴性细胞的比例仅增加了 3%。总体而言,本研究结果表明,miR-204-5p 的过表达可以在很大程度上减轻 DTIC 处理的细胞中的细胞凋亡,而不是促进它们在细胞周期的 G0 期过渡以响应化疗药物诱导的应激。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3b0/10208032/6f158f0d2939/OncolRes-29-25816-f001.jpg

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