miR-601 通过靶向 HDAC6 抑制食管鳞癌（ESCC）的增殖和转移。
MiR-601 inhibits the proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) by targeting HDAC6.
机构信息
Intensive Care Unit, Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1069-1076. doi: 10.26355/eurrev_201902_16995.
OBJECTIVE
The aim of this study was to explore the role of microRNA-601 (miR-601) in the proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells, thereby providing new thoughts for prognosis evaluation and targeted therapy of ESCC.
PATIENTS AND METHODS
23 pairs of ESCC tissue samples and adjacent normal tissues were collected, and the expression level of miR-601 was detected. Biological information analysis and Luciferase report gene assay were used to verify the potential target genes of miR-601. Then, three groups were established in ESCC cell line (TE-1) to perform similar experiments, including the miR-NC group, the miR-601 mimics group and the mimics + HDAC6 group. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation ability. Meanwhile, transwell assay and scratch-wound assay were applied to observe the effect of miR-601 on cell invasion and migration. Quantitative reverse transcription Polymerase Chain Reaction (qPCR) and Western blot assay were applied to determine the mRNA and protein expression changes after transfection.
RESULTS
Compared with normal adjacent tissues and normal esophageal epithelial cells, the expression of miR-601 was significantly decreased in ESCC tissues and cells. HDAC6 was identified as a target gene of miR-601. The expression of HDAC6 in esophageal carcinoma cells transfected with miR-601 mimics was significantly down-regulated. The negative correlation between miR-601 and HDAC6 expression was assessed by qPCR and Western blot (WB) assay. Furthermore, miR-601 remarkably suppressed the proliferation of ESCC cells. Meanwhile, cell invasion and migration were also found markedly restricted after transfection of miR-601 mimics. However, the overexpression of HDAC6 significantly counteracted the effects of miR-601.
CONCLUSIONS
MiR-601 suppressed the proliferation, invasion and migration of esophagus carcinoma cells by down-regulating HDAC6 expression.
目的
本研究旨在探讨 microRNA-601（miR-601）在食管鳞状细胞癌（ESCC）细胞增殖和侵袭中的作用，为 ESCC 的预后评估和靶向治疗提供新的思路。
方法
收集 23 对 ESCC 组织标本及癌旁正常组织，检测 miR-601 的表达水平。采用生物信息学分析和荧光素酶报告基因实验验证 miR-601 的潜在靶基因。然后，在 ESCC 细胞系（TE-1）中建立三组进行类似实验，包括 miR-NC 组、miR-601 模拟物组和模拟物+HDAC6 组。细胞计数试剂盒-8（CCK-8）检测细胞增殖能力。同时，Transwell 实验和划痕实验观察 miR-601 对细胞侵袭和迁移的影响。采用实时定量逆转录聚合酶链反应（qPCR）和 Western blot 检测转染后 mRNA 和蛋白表达变化。
结果
与正常相邻组织和正常食管上皮细胞相比，ESCC 组织和细胞中 miR-601 的表达明显降低。HDAC6 被鉴定为 miR-601 的靶基因。转染 miR-601 模拟物的食管癌细胞中 HDAC6 的表达明显下调。通过 qPCR 和 Western blot（WB）检测评估 miR-601 与 HDAC6 表达之间的负相关。此外，miR-601 显著抑制 ESCC 细胞的增殖。同时，转染 miR-601 模拟物后细胞侵袭和迁移也明显受到限制。然而，HDAC6 的过表达显著抵消了 miR-601 的作用。
结论
miR-601 通过下调 HDAC6 表达抑制食管癌细胞的增殖、侵袭和迁移。
Zotero 插件