抑癌基因调控的致癌靶点对胰腺导管腺癌的影响。
Impact of Oncogenic Targets Controlled by Tumor-Suppressive in Pancreatic Ductal Adenocarcinoma.
机构信息
Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
出版信息
Anticancer Res. 2021 Oct;41(10):4821-4836. doi: 10.21873/anticanres.15297.
BACKGROUND/AIM: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regarding the pathogenesis of this disease.
MATERIALS AND METHODS
In silico analyses were used to identify the putative target genes of miR-30a-5p and assess their expression levels. Direct regulation of RRM2 by miR-30a-5p and its oncogenic functions were evaluated in PDAC cell lines. Overexpression of RRM2 was demonstrated in clinical samples.
RESULTS
A total of 24 putative targets were identified by in silico database analysis. High expression of 4 genes (CBFB, RRM2, AHNAK, and DCBLD1) was significantly associated with shorter survival of patients with PDAC. Functional assays demonstrated that knockdown of RRM2 attenuated the malignant phenotype of PDAC cells.
CONCLUSION
The miR-30a-5p/RRM2 axis facilitated the malignant transformation of PDAC cells.
背景/目的：我们最近的 miRNA 分析表明，miR-30a-5p 在胰腺导管腺癌 (PDAC) 中具有肿瘤抑制活性。在此，我们试图确定受 miR-30a-5p 调控的肿瘤抑制基因，重点关注那些与 PDAC 分子发病机制密切相关的基因。我们发现了一些关于该疾病发病机制的新发现。
材料和方法
通过计算机分析来鉴定 miR-30a-5p 的可能靶基因，并评估它们的表达水平。在 PDAC 细胞系中评估 miR-30a-5p 对 RRM2 的直接调控及其致癌功能。在临床样本中证明了 RRM2 的过表达。
结果
通过计算机数据库分析共鉴定出 24 个可能的靶基因。4 个基因（CBFB、RRM2、AHNAK 和 DCBLD1）的高表达与 PDAC 患者的生存时间缩短显著相关。功能分析表明，RRM2 的敲低可减弱 PDAC 细胞的恶性表型。
结论
miR-30a-5p/RRM2 轴促进了 PDAC 细胞的恶性转化。
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