miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma
miR-143 inhibits tumor progression by targeting FAM83F in esophageal squamous cell carcinoma
复制标题
DOI：
10.1007/s13277-015-4760-9
复制
发表时间：
2016-07-01
期刊：
影响因子：
--
通讯作者：
Li, Baosheng
中科院分区：
文献类型：
--
作者：
Mao, Yu;Liu, Jia;Li, Baosheng
序列相似性83家族（FAM 83）成员在多种肿瘤的发生和发展中起重要作用。然而，癌细胞调节FAM 83 F的机制仍不清楚。在这项研究中，我们发现，FAM 84 F蛋白和信使RNA（mRNA）水平一致上调，在食管鳞状细胞癌（ESCC）组织中，这表明转录后机制可能参与FAM 83 F的调节。由于microRNA（miRNAs）是基因表达的强大转录后调节因子，我们进行了生物信息学分析以寻找可能靶向FAM 83 F的miRNAs。我们确定了miR-143在FAM 83 F的3 '-非翻译区（3'-UTR）中的特异性靶向位点，并证实了ESCC组织样本中miR-143和FAM 83 F蛋白和mRNA水平之间的负相关性。通过在ESCC细胞中过表达或沉默miR-143，我们实验验证了miR-143直接结合FAM 83 F转录物的3 '-UTR并降解FAM 83 F mRNA以调节FAM 83 F表达。此外，使用体外细胞增殖、凋亡、迁移和侵袭测定来检查miR-143通过靶向FAM 83 F介导的生物学后果。我们证明miR-143通过抑制ESCC细胞的增殖、迁移和侵袭，并通过负调节FAM 83 F表达诱导G1/G 0期阻滞而发挥肿瘤抑制作用。总之，我们的发现提供了重要的证据，支持miR-143通过抑制FAM 83 F表达在ESCC中作为肿瘤抑制因子的作用。
Family with sequence similarity 83 (FAM83) members play important roles in carcinogenesis and tumor progression in several tumor types. However, the mechanism by which cancer cells regulate FAM83F still remains unclear. In this study, we found that the FAM84F protein and messenger RNA (mRNA) levels were consistently upregulated in esophageal squamous cell carcinoma (ESCC) tissues, which suggests that a post-transcriptional mechanism may be involved in the regulation of FAM83F. Since microRNAs (miRNAs) are powerful post-transcriptional regulators of gene expression, we performed bioinformatic analyses to search for miRNAs that could potentially target FAM83F. We identified the specific targeting site of miR-143 in the 3'-untranslated region (3'-UTR) of FAM83F and confirmed the inverse correlation between the levels of miR-143 and FAM83F protein and mRNA in ESCC tissue samples. By overexpressing or silencing miR-143 in ESCC cells, we experimentally validated that miR-143 directly binds to the 3'-UTR of the FAM83F transcript and degrades the FAM83F mRNA to regulate FAM83F expression. Furthermore, the biological consequences that miR-143 mediated by targeting FAM83F were examined using in vitro cell proliferation, apoptosis, migration, and invasion assays. We demonstrate that miR-143 exerted a tumor-suppressing effect by inhibiting the proliferation, migration, and invasion and inducing G1/G0 phase arrest of ESCC cells via the negative regulation of FAM83F expression. Taken together, our findings provide important evidence which supports the role of miR-143 as a tumor suppressor in ESCC via the inhibition of FAM83F expression.