Chen Hongxi, Zhang Zhipeng, Lu Yebin, Song Kun, Liu Xiwu, Xia Fada, Sun Weijia
Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.
Cancer Sci. 2017 Sep;108(9):1811-1819. doi: 10.1111/cas.13315. Epub 2017 Aug 10.
Dysregulation of microRNA (miRNA) expression in various cancers and their role in cancer progression is well documented. The purpose of this study was to investigate the biological role of miR-372 in human pancreatic adenocarcinoma (HPAC). We collected 20 pairs of HPAC tissues and adjacent non-cancerous tissues to detect miR-372 expression levels. We transfected BXPC-3 and PANC-1 cells with miR-372 inhibitor/mimics to study their effect on cell proliferation, apoptosis, invasion, migration and autophagy. In addition, miR-372 mimics and a tumor protein UNC51-like kinase 1 (ULK1) siRNA were co-transfected into BXPC-3 and PANC-1 cells to explore the mechanism of miR-372 and ULK1 on HPAC tumorigenesis. We found that the expression of miR-372 was markedly downregulated in HPAC cells compared to adjacent normal tissues. Furthermore, functional assays showed that miR-372 inhibited cell proliferation, invasion, migration and autophagy in BXPC-3 and PANC-1 cells. An inverse correlation between miR-372 expression and ULK1 expression was observed in HPAC tissues. Downregulation of ULK1 inhibited the overexpression effects of miR-372, and upregulation of ULK1 reversed the effects of overexpressed miR-372. Finally, we found that silencing ULK1 or inhibiting autophagy partly rescued the effects of miR-372 knockdown in HPAC cells, which may explain the influence of miR-372/ULK1 in HPAC development. Taken together, these results revealed a significant role of the miR-372/ULK1 axis in suppressing HPAC cell proliferation, migration, invasion and autophagy.
微小RNA（miRNA）表达失调在各种癌症中的情况及其在癌症进展中的作用已有充分记载。本研究的目的是探讨miR-372在人胰腺腺癌（HPAC）中的生物学作用。我们收集了20对HPAC组织和相邻的非癌组织，以检测miR-372的表达水平。我们用miR-372抑制剂/模拟物转染BXPC-3和PANC-1细胞，以研究其对细胞增殖、凋亡、侵袭、迁移和自噬的影响。此外，将miR-372模拟物和肿瘤蛋白UNC51样激酶1（ULK1）小干扰RNA共转染到BXPC-3和PANC-1细胞中，以探索miR-372和ULK1对HPAC肿瘤发生的作用机制。我们发现，与相邻正常组织相比，HPAC细胞中miR-372的表达明显下调。此外，功能分析表明，miR-372抑制BXPC-3和PANC-1细胞的增殖、侵袭、迁移和自噬。在HPAC组织中观察到miR-372表达与ULK1表达呈负相关。ULK1的下调抑制了miR-372的过表达效应，而ULK1的上调则逆转了过表达miR-372的效应。最后，我们发现沉默ULK1或抑制自噬部分挽救了HPAC细胞中miR-372敲低的效应，这可能解释了miR-372/ULK1在HPAC发展中的影响。综上所述，这些结果揭示了miR-372/ULK1轴在抑制HPAC细胞增殖、迁移、侵袭和自噬中的重要作用。
