MicroRNA (miR)−141‐3p, which functions as an oncogene in multiple malignancies, has been shown to be highly overexpressed in esophageal cancer cells in our previous work. miR‐141‐3p is predicted to bind the messenger RNA (mRNA) of tuberous sclerosis complex 1 (TSC1), a tumor suppressor, with high affinity. In this study, we investigated the expression and functional interaction between miR‐141‐3p and TSC1 in esophageal cancer cells. Experiments were conducted in four esophageal cancer lines and in tumor cells isolated from human esophageal cancer specimens by laser capture microdissection. miR‐141‐3p expression was measured by real time and droplet digital PCR. Biotinylated RNA pull‐down and luciferase reporter assays were used to assess binding. miR‐141‐3p function was tested by assessing proliferation, migration, invasion, and induction of autophagy following its silencing. We found that miR‐141‐3p levels were increased in TE7, OE33, and TE10 esophageal cancer cells compared to FLO‐1 cells, with similar heterogeneity observed in human esophageal cancer specimens. Silencing of miR‐141‐3p led to increased TSC1 protein expression in these cells and was associated with increased TSC1 translation. Binding studies reveal that miR‐141‐3p binds to each of the predicted binding sites in the 3′‐untranslated region of TSC1 mRNA. Following miR‐141‐3p silencing, TE7, OE33, and TE10 cells exhibited decreased proliferation, migration, and invasion, as well as enhanced autophagy. Importantly, these phenotypic effects were replicated by overexpression of TSC1 alone in these cells. Our results indicate that miR‐141‐3p functions in an oncogenic capacity in a subset of esophageal cancer cells, in part by suppressing TSC1 expression.

中文翻译：

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MicroRNA‐141‐3p通过靶向结节性硬化复合物1来调节食道癌中的细胞增殖，迁移和侵袭

MicroRNA（miR）−141-3p在多种恶性肿瘤中起着癌基因的作用，在我们以前的研究中已显示在食道癌细胞中高度过表达。预计miR‐141-3p与肿瘤抑制因子结节性硬化复合物1（TSC1）的信使RNA（mRNA）具有高亲和力。在这项研究中，我们研究了食管癌细胞中miR‐141‐3p和TSC1之间的表达和功能相互作用。实验是在四种食道癌细胞系和通过激光捕获显微切割从人食道癌标本中分离的肿瘤细胞中进行的。通过实时和液滴数字PCR测量miR‐141‐3p表达。使用生物素化的RNA下拉和荧光素酶报告基因分析法评估结合。通过评估增殖，迁移，侵袭，沉默后诱导自噬。我们发现，与FLO-1细胞相比，TE7，OE33和TE10食管癌细胞中的miR-141-3p水平升高，在人类食道癌标本中观察到相似的异质性。miR‐141‐3p沉默导致这些细胞中TSC1蛋白表达增加，并与TSC1翻译增加有关。结合研究表明，miR‐141-3p与TSC1 mRNA 3'非翻译区中的每个预测结合位点结合。在miR‐141-3p沉默后，TE7，OE33和TE10细胞表现出减少的增殖，迁移和侵袭，并增强了自噬。重要的是，这些表型效应是通过在这些细胞中单独过表达TSC1来复制的。