miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts.
miR-31 affects colorectal cancer cells by inhibiting autophagy in cancer-associated fibroblasts.
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miR-31通过抑制癌症相关成纤维细胞的自噬来影响结直肠癌细胞
DOI：
10.18632/oncotarget.12873
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发表时间：
2016-11-29
期刊：
影响因子：
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通讯作者：
Peng W
中科院分区：
文献类型：
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作者：
Yang X;Xu X;Zhu J;Zhang S;Wu Y;Wu Y;Zhao K;Xing C;Cao J;Zhu H;Li M;Ye Z;Peng W
自噬在肿瘤发生发展中是一把双刃剑。最近的研究发现，miRNAs对自噬的调控具有抑制作用。已有研究表明miR-31在结直肠癌的发生发展中起重要作用。然而，miR-31在结直肠癌相关成纤维细胞（CAF）中的作用尚未确定。在这项研究中，我们证实了miR-31在CAFs中的表达高于正常结直肠成纤维细胞（NF）。我们还发现，用miR-31模拟物处理CAFs抑制了自噬相关基因Beclin-1、ATG、DRAM和LC 3的表达。此外，我们发现miR-31的上调显著影响结直肠癌细胞的行为，包括增殖、侵袭和凋亡。同时，上调CAF中miR-31表达可增加与CAF共培养的结直肠癌细胞的放射敏感性。总之，miR-31可以抑制结直肠CAF中的自噬，影响结直肠癌的发展，并增加与CAF共培养的结直肠癌细胞的放射敏感性。我们推测miR-31可能成为结直肠癌治疗的新靶点。
Autophagy is a double-edged sword in tumor development. Recent studies have found that miRNAs have an inhibitory effect on the regulation of autophagy. It has been reported that miR-31 plays an important role in the development of colorectal cancer. However, what role miR-31 plays in colorectal cancer-associated fibroblasts (CAFs) has not been determined. In this study, we confirmed that the expression of miR-31 in CAFs was higher than in normal colorectal fibroblasts (NFs). We also found that treatment of CAFs with miR-31 mimic inhibited the expression of the autophagy-related genes Beclin-1, ATG, DRAM and LC3. In addition, we found up-regulation of miR-31 significantly affected colorectal cancer cell behaviors, including proliferation, invasion and apoptosis. Also, up-regulation of miR-31 in CAF could increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. In summary, miR-31 can inhibit autophagy in colorectal CAFs, affect colorectal cancer development, and increase the radiosensitivity of colorectal cancer cells co-cultured with CAF. We hypothesize that miR-31 may become a new target of treatments for colorectal cancer.