Xing Xiaojing, Gu Xiaohu, Ma Tianfei
Cancer Prevention and Treatment Office, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Department of Surgical Oncology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7538-44. doi: 10.3892/mmr.2015.4383. Epub 2015 Sep 29.
Biglycan is an important component of the extracellular matrix, and it is also a member of small leucine-rich proteoglycan family. Previous studies indicated that the expression of biglycan was increased in a variety of tumor tissues, including colon cancer. However, the mechanisms underlying its effects in colon cancer remain to be fully elucidated. In the present study, the effects of biglycan knockdown on colon cancer cell proliferation, migration, invasion and apoptosis were investigated. The mRNA expression levels of biglycan in the HCT116 colon cancer cell line were downregulated using RNA interference, and the stably transfected cell line was obtained through G418 screening for subsequent experiments. The results revealed that downregulation of the expression of biglycan suppressed cell proliferation and caused a cell cycle arrest at the G0/G1 phase. The results of the western blot analysis also revealed that the expression levels of cell cycle‑associated proteins, including cyclin A and cyclin D1, were markedly decreased following silencing of biglycan, whereas the expression levels of p21 and p27 were markedly increased compared with that of the short hairpin RNA control group. Furthermore, the decreased expression of biglycan inhibited colon cancer cell migration and invasion, and induced apoptosis. A complete inhibition of the p38 signaling pathway with SB203580 effectively reversed the increase in apoptotic cell numbers induced by biglycan downregulation. Taken together, the results of the present study indicated that biglycan exerts an important role in cell proliferation, migration, invasion and apoptosis in colon cancer, and that biglycan regulates the p38 MAPK signaling pathway by exerting an antiapoptotic effect. Therefore, biglycan may represent a putative target for colon cancer gene therapy.
双糖链蛋白聚糖是细胞外基质的重要组成部分，也是富含亮氨酸的小分子蛋白聚糖家族的成员。先前的研究表明，双糖链蛋白聚糖在包括结肠癌在内的多种肿瘤组织中的表达增加。然而，其在结肠癌中发挥作用的机制仍有待充分阐明。在本研究中，研究了双糖链蛋白聚糖敲低对结肠癌细胞增殖、迁移、侵袭和凋亡的影响。使用RNA干扰下调HCT116结肠癌细胞系中双糖链蛋白聚糖的mRNA表达水平，并通过G418筛选获得稳定转染的细胞系用于后续实验。结果显示，双糖链蛋白聚糖表达下调抑制了细胞增殖，并导致细胞周期停滞在G0/G1期。蛋白质印迹分析结果还显示，双糖链蛋白聚糖沉默后，细胞周期相关蛋白包括细胞周期蛋白A和细胞周期蛋白D1的表达水平显著降低，而与短发夹RNA对照组相比，p21和p27的表达水平显著升高。此外，双糖链蛋白聚糖表达降低抑制了结肠癌细胞的迁移和侵袭，并诱导了凋亡。用SB203580完全抑制p38信号通路有效地逆转了双糖链蛋白聚糖下调诱导的凋亡细胞数量增加。综上所述，本研究结果表明，双糖链蛋白聚糖在结肠癌的细胞增殖、迁移、侵袭和凋亡中发挥重要作用，并且双糖链蛋白聚糖通过发挥抗凋亡作用调节p38 MAPK信号通路。因此，双糖链蛋白聚糖可能是结肠癌基因治疗的一个假定靶点。
