MicroRNA-152 inhibits tumor cell growth while inducing apoptosis via the transcriptional repression of cathepsin L in gastrointestinal stromal tumor (Retracted article. See vol. 35, pg. 343, 2022)
MicroRNA-152 inhibits tumor cell growth while inducing apoptosis via the transcriptional repression of cathepsin L in gastrointestinal stromal tumor (Retracted article. See vol. 35, pg. 343, 2022)
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DOI：
10.3233/cbm-170809
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发表时间：
2018-01-01
影响因子：
3.1
通讯作者：
Zheng, Yuan-Lin
中科院分区：
文献类型：
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作者：
Lu, Hong-Jie;Yan, Jing;Zheng, Yuan-Lin
目的：MicroRNA被广泛认为在基因表达中起调控作用。虽然在几种肿瘤中已经报道了更独特的microRNA表达谱，但仍然缺乏与GIST中microRNA表达谱相关的知识。在本研究中，通过改变胃肠道间质瘤（GIST）细胞中microRNA-152（miR-152）的表达，我们随后评估了其影响肿瘤相关过程的能力，包括增殖、迁移、侵袭和凋亡，以及相关机制。检测miR-152和组织蛋白酶L（CTSL）在GIST细胞系（GIST 882、GIST 430、GIST 48和GIST-T1）和正常胃粘膜细胞系RGM-1中的表达。引入一系列miR-152模拟物、miR-152抑制剂和针对CTSL的siRNA来处理GIST-T1细胞，评估最低的miR-152和最高的CTSL。通过CCK-8法、Annexin V-FITC/PI染色流式细胞仪分析和transwell法检测细胞活力、细胞周期进入、凋亡和细胞迁移/侵袭能力。关于miR-152的生物学意义，siRNA敲低和异位表达研究显示，miR-152模拟物或针对CTSL的siRNA暴露降低细胞活力和迁移/侵袭，这导致更多的细胞停滞在S期，并诱导凋亡。观察到miR-152抑制剂暴露对CTSL细胞具有诱导作用，这与miR-152模拟物诱导的作用相反。相反，miR-152的下调可阻断siRNA对CTSL治疗的作用。结论：miR-152通过与CTSL结合诱导GIST细胞凋亡，抑制GIST细胞增殖、迁移和侵袭。miR-152的抗肿瘤作用使其成为GIST的有吸引力的治疗靶点。
OBJECTIVE: MicroRNAs are widely thought to play a regulatory role in gene expression. Although the more unique microRNA expression profiles have been reported in several tumors, there remains a scarcity of knowledge in relation to microRNA expression profiles in GISTs. During this study, through the alteration in the expression of microRNA-152 (miR-152) in gastrointestinal stromal tumor (GIST) cells, we subsequently evaluated its ability to influence the processes associated with cancer, including proliferation, migration, invasion, and apoptosis, as well as the associated mechanisms.METHODS: The expression of miR-152 and cathepsin L (CTSL) in GIST cell lines (GIST882, GIST430, GIST48 and GIST-T1) and normal gastric mucosal cell line RGM-1 were determined. A series of miR-152 mimics, miR-152 inhibitors, and siRNA against CTSL were introduced to treat GIST-T1 cells with the lowest miR-152 and the highest CTSL were assessed. Cell viability, cell cycle entry, apoptosis, and cell migration/invasion were all evaluated by means of CCK-8 assay, flow cytometry analyses of Annexin V-FITC/PI staining, and transwell assays.RESULTS: The target prediction program and luciferase reporter gene assay verified CTSL is the target of miR-152. Regarding the biological significance of miR-152, siRNA knockdown and ectopic expression studies revealed that miR-152 mimic or siRNA against CTSL exposure reduced cell viability and migration/invasion, which resulted in more cells arrested at the S stage, and induced apoptosis. MiR-152 inhibitor exposure was observed to have induced effects on CTSL cells as opposed to those induced by that of the miR-152 mimics. In contrast, miR-152 downregulation abrogated the effects induced by siRNA against CTSL treatment.CONCLUSION: The key findings of this study provided evidence suggesting that miR-152 functions by means of binding to CTSL to induce GIST cell apoptosis and inhibit proliferation, migration, and invasion. The anti-tumor role of miR-152 makes it an attractive therapeutic target for GIST.