Yu Yifan, Liu Dongliang, Liu Zhenghao, Li Shuqiang, Ge Yang, Sun Wei, Liu Baolin
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Ear-nose-throat department, Shengjing Hospital of China Medical University, Shenyang, China.
J Cancer. 2018 Jul 30;9(16):2953-2962. doi: 10.7150/jca.25542. eCollection 2018.
Collagen type I alpha 2 chain (COL1A2) has been shown to participate in the development of various human malignancies. However, the role of COL1A2 in human colorectal cancer (CRC) remains unknown. This study investigated the expression pattern of COL1A2 in primary CRC tissues as well as the correlation of COL1A2 expression with clinicopathological features and prognosis of CRC. The function of COL1A2 in CRC cell proliferation, migration, and invasion as well as the possible mechanisms were also examined. Real-time PCR and immunohistochemical analysis were performed to determine the expression of COL1A2 in primary cancer tissues and adjacent normal tissues from CRC patients. A COL1A2-expressing lentiviral vector was transfected into CRC cells, and cell counting kit-8 and Transwell assays were used to explore the effects of COL1A2 on CRC cell proliferation, migration, and invasion. Microarray-based mRNA expression profile screening was performed to reveal the possible signaling pathways involved in COL1A2-regulated cell behaviors. COL1A2 was significantly downregulated in primary CRC tissues. The mRNA levels of COL1A2 in CRC tissues were correlated with tumor differentiation, invasion, and lymph node metastasis. Overexpression of COL1A2 inhibited proliferation, migration, and invasion of CRC cell lines (SW480 and SW620). The microarray analysis showed that COL1A2 overexpression regulated numerous oncogenes and cancer-related signaling pathways. Among them, altered expression of ten representative cancer-related genes in these pathways were further confirmed by western blotting. Our study identified COL1A2 as a novel tumor suppressor in CRC and provided a potential therapeutic approach to treat CRC.
I型胶原蛋白α2链（COL1A2）已被证明参与多种人类恶性肿瘤的发生发展。然而，COL1A2在人类结直肠癌（CRC）中的作用仍不清楚。本研究调查了COL1A2在原发性CRC组织中的表达模式，以及COL1A2表达与CRC临床病理特征和预后的相关性。还检测了COL1A2在CRC细胞增殖、迁移和侵袭中的作用及其可能机制。采用实时PCR和免疫组化分析确定COL1A2在CRC患者原发性癌组织和癌旁正常组织中的表达。将表达COL1A2的慢病毒载体转染到CRC细胞中，并用细胞计数试剂盒-8和Transwell实验探讨COL1A2对CRC细胞增殖、迁移和侵袭的影响。通过基于微阵列的mRNA表达谱筛选揭示COL1A2调节细胞行为可能涉及的信号通路。COL1A2在原发性CRC组织中显著下调。CRC组织中COL1A2的mRNA水平与肿瘤分化、侵袭和淋巴结转移相关。COL1A2的过表达抑制了CRC细胞系（SW480和SW620）的增殖、迁移和侵袭。微阵列分析表明，COL1A2的过表达调节了许多癌基因和癌症相关信号通路。其中，通过蛋白质印迹进一步证实了这些通路中十个代表性癌症相关基因的表达改变。我们的研究确定COL1A2是CRC中的一种新型肿瘤抑制因子，并为治疗CRC提供了一种潜在的治疗方法。
