Hou Ni, Han Jia, Li Jie, Liu Yingxun, Qin Yannan, Ni Lei, Song Tusheng, Huang Chen
Department of Genetics and Molecular Biology, Xi'an Jiaotong University School of Medicine, Xi'an, China.
Department of General Surgery, the Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, China.
PLoS One. 2014 Dec 19;9(12):e114779. doi: 10.1371/journal.pone.0114779. eCollection 2014.
Autophagy modulation is now recognized as a potential therapeutic approach for cancer (including colorectal cancer), yet the molecular mechanisms regulating autophagy in response to cellular stress are still not well understood. MicroRNAs (miRNAs) have been found to play important roles in controlling many cellular functions, including growth, metabolism and stress response. The physiological importance of the miRNA-autophagy interconnection is only beginning to be elucidated. MiRNA microarray technology facilitates analysis of global miRNA expression in certain situations. In this study, we explored the expression profile of miRNAs during the response of human colon cancer cells (HT29s) to 5-FU treatment and nutrient starvation using miRNA microarray analysis. The alteration of miRNA expression showed the same pattern under both conditions was further testified by qRT-PCR in three human colon cancer cell lines. In addition, bioinformatic prediction of target genes, pathway analysis and gene network analysis were performed to better understand the roles of these miRNAs in the regulation of autophagy. We identified and selected four downregulated miRNAs including hsa-miR-302a-3p and 27 upregulated miRNAs under these two conditions as having the potential to target genes involved in the regulation of autophagy in human colon cancer cells. They have the potential to modulate autophagy in 5-FU-based chemotherapy in colorectal cancer.
自噬调节目前被认为是一种针对癌症（包括结直肠癌）的潜在治疗方法，然而，响应细胞应激调节自噬的分子机制仍未得到充分理解。已发现微小RNA（miRNA）在控制许多细胞功能中发挥重要作用，包括生长、代谢和应激反应。miRNA与自噬相互联系的生理重要性才刚刚开始被阐明。miRNA微阵列技术有助于在特定情况下分析全局miRNA表达。在本研究中，我们使用miRNA微阵列分析探讨了人结肠癌细胞（HT29）对5-氟尿嘧啶治疗和营养饥饿反应期间miRNA的表达谱。在两种条件下miRNA表达的改变显示出相同模式，这在三种人结肠癌细胞系中通过qRT-PCR进一步得到证实。此外，进行了靶基因的生物信息学预测、通路分析和基因网络分析，以更好地理解这些miRNA在自噬调节中的作用。我们鉴定并选择了在这两种条件下四个下调的miRNA，包括hsa-miR-302a-3p和27个上调的miRNA，它们有可能靶向参与人结肠癌细胞自噬调节的基因。它们有可能在结直肠癌基于5-氟尿嘧啶的化疗中调节自噬。
