miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma.

miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma.
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DOI:
10.7717/peerj.10020
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发表时间:
2021
期刊:
影响因子:
2.7
通讯作者:
Zhan Q
Zhan Q
中科院分区:
生物学3区
文献类型:
--
作者:
Kang N;Ou Y;Wang G;Chen J;Li D;Zhan Q

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食管鳞状细胞癌(ESCC)是全球癌症死亡的主要原因之一。目前,缺乏诊断和治疗ESCC的有效遗传标记。MicroRNAs (miRNAs)是一种全球性的遗传调节剂,通过结合靶向mrna的3 ‘非翻译区(3 ’ utr)来控制癌症基因的表达。此外,miRNAs在肿瘤的发展过程中作为癌基因或肿瘤抑制因子发挥作用。在目前的研究中,我们发现根据TCGA数据库,hsa-miR-875-5p (miR-875-5p)在ESCC中表现出扩增。然后,采用xCELLigence实时细胞分析仪(RTCA)-MP系统和集落形成法检测细胞增殖和集落形成能力。结果显示miR-875-5p促进ESCC细胞增殖。随后,transwell结果表明,miR-875-5p促进了ESCC细胞的侵袭和迁移。此外,我们发现miR-875-5p能够结合CAPZA13'UTR, CAPZA13'UTR含有单核苷酸多态性(SNP) rs373245753,正如我们之前在WGS和WES对ESCC的研究中报道的那样。随后,mRNA亲和力下拉试验证实该SNP破坏了miR-875-5p与CAPZA1的结合。目前的研究首次证明miR-875-5p可能通过下调ESCC中CAPZA1的表达而发挥致癌基因的作用。
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3′untranslated regions (3′UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently, transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13’UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 expression in ESCC.
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