miR-338-3p suppresses colorectal cancer proliferation and progression by inhibiting MACC1
miR-338-3p suppresses colorectal cancer proliferation and progression by inhibiting MACC1
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miR-338-3p 通过抑制 MACC1 抑制结直肠癌增殖和进展
DOI：
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Anjia Han
中科院分区：
文献类型：
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作者：
Teng Zou;Jing Duan;Jiangtao Liang;Huijuan Shi;Tiantian Zhen;Hui Li;Fenfen Zhang;Yu Dong;Anjia Han
摘要：结直肠癌（CRC）是全球最常见的恶性肿瘤之一。本研究旨在阐明miR-338- 3 p在结直肠癌中的临床病理学意义及其与结肠癌转移相关蛋白1（MACC 1）的关系。我们评估了miR-338- 3 p和MACC 1在CRC细胞系中的表达，并分析了98例CRC组织样本中miR-338- 3 p的临床病理特征。随后进行Western印迹和细胞生物学技术以及异种移植小鼠模型以研究miR-338- 3 p在CRC中的生物学作用及其与MACC 1的关联。我们的研究结果表明，miR-338- 3 p在CRC细胞系和组织中的表达分别低于人正常结肠上皮细胞系和邻近正常结肠直肠组织。miR-338- 3 p的表达与98例大肠癌的组织学分化、UICC分期、T分型、N分型和M分型显著相关。低miR-338- 3 p表达组的CRC患者的总生存率显著低于高miR-338 - 3 p表达组（p<0.01）。miR-338- 3 p模拟物抑制细胞增殖、集落形成、迁移和侵袭，但诱导CRC细胞凋亡。miR-338- 3 p抑制剂逆转了这些生物学表型。miR-338- 3 p模拟物或抑制剂抑制或增加HCT 116和SW 620中的MACC 1表达。miR-338- 3 p模拟物逆转了由具有MACC 1过表达质粒的HCT 116诱导的MACC 1表达增加的效应。在用miR-338- 3 p模拟物转染的HCT 116中，由MACC 1过表达引起的细胞增殖增加、集落形成和细胞凋亡抑制分别被显著逆转。在转染miR-338- 3 p抑制剂的SW 620中，MACC 1敲低导致的细胞增殖、集落形成、迁移、侵袭和细胞凋亡增加分别被显著逆转。在体内，miR-338- 3 p agomir显著抑制了异种移植CRC肿瘤生长，并逆转了由具有MACC 1过表达的HCT 116诱导的异种移植肿瘤生长增加的效应。总之，我们的数据表明，miR-338- 3 p通过抑制MACC 1抑制CRC癌的发生和进展。靶向miR-338- 3 p可能是一种新的CRC治疗策略。
Abstract: Colorectal cancer (CRC) is one of the most common malignancies worldwide. This study aimed to elucidate the clinicopathological significance of miR-338-3p and its association with metastasis-associated in colon cancer-1 (MACC1) in CRC. We evaluated miR-338-3p and MACC1 expression in CRC cell lines and analyzed the clinicopathological features of miR-338-3p in 98 samples of CRC tissues. Subsequent Western blot and cellular biological techniques, and xenograft mouse models were performed to investigate the biological role of miR-338-3p and its association with MACC1 in CRC. Our results show that miR-338-3p expression is lower in CRC cell lines and tissues than that in a human normal colonic epithelial cell line and adjacent normal colorectal tissue, respectively. miR-338-3p expression was significantly associated with histological differentiation, UICC stage, T classification, N classification, and M classification in 98 samples of CRC. The overall survival of CRC patients was significantly less in the low miR-338-3p expression group than in the high miR-338-3p expression group (p<0.01). miR-338-3p mimics suppressed cell proliferation, colony formation, migration, and invasion, but induced apoptosis in CRC cells. miR-338-3p inhibitor reversed these biological phenotypes. miR-338-3p mimics or inhibitor suppressed or increased MACC1 expression in HCT116 and SW620. miR-338-3p mimics reversed the effect of increased MACC1 expression induced by HCT116 with MACC1 over-expression plasmid. Increased cell proliferation, colony formation, and suppressed cell apoptosis caused by MACC1 over-expression were significantly reversed in HCT116 transfected with miR-338-3p mimics, respectively. Suppressed cell proliferation, colony formation, migration, invasion, and increased cell apoptosis caused by MACC1 knockdown were significantly reversed in SW620 transfected with miR-338-3p inhibitor, respectively. In vivo, miR-338-3p agomir significantly inhibited xenograft CRC tumor growth and reversed the effect of increased xenograft tumor growth induced from HCT116 with MACC1 overexpression. In conclusion, our data suggest that miR-338-3p suppresses CRC carcinogenesis and progression by inhibiting MACC1. Targeting miR-338-3p might be a novel treatment strategy for CRC.