Zhang Yajing, Tang Xiaomei, Shi Minmin, Wen Chenlei, Shen Baiyong
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
Biochem Biophys Res Commun. 2017 Feb 5;483(2):816-822. doi: 10.1016/j.bbrc.2016.12.167. Epub 2016 Dec 26.
How lncRNA MALAT1 is regulated by miRNAs at posttranscriptional level in pancreatic cancer and their regulative effects on the cancer cells remain largely unknown. By retrieving previous miRNA array data and performing primary qRT-PCR, we observed a significant negative correlation between miR-216a and MALAT1 in pancreatic ductal adenocarcinoma (PDAC) tissues and adjacent normal tissues. The following in vitro cell assay further confirmed a direct binding between miR-216a and MALAT1 and the suppressive effect of miR-216a on MALAT1 expression. MiR-216a overexpression had similar effects as MALAT1 siRNA on restoring p21 and p27 expression and inhibiting B-MYB, RAF1 and PCNA1 expression in both PANC-1 and BxPC3 cells. MiR-216a overexpression and MALAT1 knockdown induced cell cycle arrest at G2/M phase. MiR-216a overexpression not only significantly induced cell apoptosis, but also reduced cell viability and increased cell apoptosis in response to gemcitabine in the cancer cells. Based on these findings, we infer that miR-216a induces apoptosis both in the presence and absence of gemcitabine in pancreatic cancer cells by silencing MALAT1 expression.
在胰腺癌中，长链非编码RNA MALAT1如何在转录后水平受微小RNA（miRNA）调控以及它们对癌细胞的调控作用在很大程度上仍不清楚。通过检索先前的miRNA芯片数据并进行初步定量逆转录聚合酶链反应（qRT-PCR），我们观察到在胰腺导管腺癌（PDAC）组织和相邻正常组织中，miR-216a与MALAT1之间存在显著的负相关。随后的体外细胞实验进一步证实了miR-216a与MALAT1之间的直接结合以及miR-216a对MALAT1表达的抑制作用。在PANC-1和BxPC3细胞中，miR-216a过表达在恢复p21和p27表达以及抑制B-MYB、RAF1和PCNA1表达方面与MALAT1小干扰RNA（siRNA）具有相似的效果。miR-216a过表达和MALAT1敲低诱导细胞周期阻滞于G2/M期。miR-216a过表达不仅显著诱导细胞凋亡，还降低细胞活力，并增强癌细胞对吉西他滨的细胞凋亡反应。基于这些发现，我们推断miR-216a在胰腺癌细胞中通过沉默MALAT1表达，在有和没有吉西他滨的情况下均诱导细胞凋亡。
