Department of Integrated Traditional Chinese and Western Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
J Invest Surg. 2021 Jun;34(6):664-669. doi: 10.1080/08941939.2019.1672839. Epub 2020 Nov 5.
Type XI collagen (COL11A1) was reported to associate with malignancy in several cancer types, whereas its role in lung cancer is not fully understood. Therefore, the present study aimed to explore the expression level and biological role of COL11A1 in lung cancer cells.
Gene Expression Omnibus (GEO) database containing 6 lung cancer tissues and normal lung tissues was used to identify potential aberrantly expressed genes. The expression of COL11A1, apoptosis related genes, cell cycle related genes and migration associated genes at the protein level were evaluated by western blot and at the mRNA level was determined by real-time PCR in lung cancer cell lines. Furthermore, the expression of COL11A1 was silenced by siRNA, and cell viability was detected by Cell counting kit-8 (CCK-8) assay. Moreover, cell apoptosis and cell cycle were determined by flow cytometry. In addition, transwell and wound-healing assay were applied to determine cell migration ability.
GEO analysis suggests that COL11A1 was highly expressed in patients with lung cancer, which was consistent with the results in lung cancer cell lines. COL11A1 knockdown in lung cancer cells significantly lowered the colony formation ability, augmented cell apoptosis rate and elevated the expression of cleaved caspase-3, cleaved caspase-9, Bax, P21 and the expression of Bcl-2, CyclinD1, CDK2 and CDK-4 was significantly downregulated (all < 0.05). Moreover, post-COL11A1 knockdown, the cell wound-healing and migration ability was significantly impaired, which also supported by the upregulation of E-Cadherin and downregulation of N-Cadherin, Vimentin and Snail (all < 0.05). Furthermore, we also found that COL11A1 knockdown decreased the expression of p-AKT, p-PI3K and p-ERK.
The present study revealed that COL11A1 may contribute to the malignancy and involve in the pathogenesis of lung cancer.
XI 型胶原（COL11A1）在多种癌症类型中与恶性肿瘤相关，但其在肺癌中的作用尚不完全清楚。因此，本研究旨在探讨 COL11A1 在肺癌细胞中的表达水平和生物学作用。
使用基因表达综合数据库（GEO）中包含的 6 例肺癌组织和正常肺组织的数据，以鉴定潜在的异常表达基因。通过 Western blot 检测 COL11A1 以及凋亡相关基因、细胞周期相关基因和迁移相关基因在蛋白水平上的表达，通过实时 PCR 检测其在肺癌细胞系中的 mRNA 水平。此外，通过 siRNA 沉默 COL11A1 的表达，通过细胞计数试剂盒-8（CCK-8）测定细胞活力。此外，通过流式细胞术检测细胞凋亡和细胞周期。另外，通过 Transwell 和划痕愈合实验测定细胞迁移能力。
GEO 分析表明，COL11A1 在肺癌患者中高表达，这与肺癌细胞系中的结果一致。在肺癌细胞中敲低 COL11A1 显著降低了集落形成能力，增加了细胞凋亡率，并上调了 cleaved caspase-3、cleaved caspase-9、Bax、P21 的表达，同时下调了 Bcl-2、CyclinD1、CDK2 和 CDK-4 的表达（均 P<0.05）。此外，COL11A1 敲低后，细胞划痕愈合和迁移能力显著受损，这也得到了 E-Cadherin 上调和 N-Cadherin、Vimentin 和 Snail 下调的支持（均 P<0.05）。此外，我们还发现 COL11A1 敲低降低了 p-AKT、p-PI3K 和 p-ERK 的表达。
本研究揭示了 COL11A1 可能有助于肺癌的恶性转化，并参与其发病机制。
