Wan Yun, Shen Aling, Qi Fei, Chu Jianfeng, Cai Qiaoyan, Sferra Thomas Joseph, Peng Jun, Chen Youqin
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
Exp Ther Med. 2017 Oct;14(4):3901-3907. doi: 10.3892/etm.2017.4972. Epub 2017 Aug 18.
MicroRNAs (miRNAs) are small, short endogenous non-coding RNA that act as oncogenes or tumor suppressors, and serve an important role in various human malignant cancers, including colorectal cancer (CRC). Evidence has indicated that miRNAs regulate the expression of various genes associated with human cancer, in particular the miR-34 family. A well-known traditional Chinese formula, Pien Tze Huang (PZH), has a significant clinical effect on CRC. Previous studies have demonstrated that PZH inhibits CRC growth and via multiple mechanisms, including the induction of apoptosis, inhibition of cell proliferation and tumor angiogenesis. To further elucidate the molecular mechanisms underlying the antitumor activity of PZH, in the present study its effects on cell proliferation and miRNA expression in human colon carcinoma (HCT)-8 cell lines was examined. It was observed that treatment with PZH inhibited cell viability and upregulated the expression of miR-34c-5p in HCT-8 cells. In addition, transfection with an miR-34c-5p mimic and treatment with PZH inhibited cell survival and arrested the cell cycle between the G0/G1 and S phase in HCT-8 cells. Furthermore, PZH treatment and transfection with miR-34c-5p downregulated the expression of cyclin-dependent kinase 4 and cMyc (a promoter of cell proliferation), and increased the expression of p53, which is a promoter of apoptosis. These results suggest that PZH may suppress proliferation in CRC cells by upregulating the expression of miR-34c-5p, which provides a novel perspective for understanding the mode of action of PZH.
微小RNA(miRNA)是一类短小的内源性非编码RNA,可作为癌基因或肿瘤抑制因子,在包括结直肠癌(CRC)在内的多种人类恶性肿瘤中发挥重要作用。有证据表明,miRNA可调节与人类癌症相关的各种基因的表达,尤其是miR-34家族。著名的传统中药片仔癀(PZH)对结直肠癌具有显著的临床疗效。先前的研究表明,PZH通过多种机制抑制结直肠癌的生长,包括诱导细胞凋亡、抑制细胞增殖和肿瘤血管生成。为了进一步阐明PZH抗肿瘤活性的分子机制,本研究检测了其对人结肠癌细胞系(HCT)-8细胞增殖和miRNA表达的影响。结果发现,PZH处理可抑制HCT-8细胞的活力,并上调miR-34c-5p的表达。此外,转染miR-34c-5p模拟物和PZH处理均可抑制HCT-8细胞的存活,并使细胞周期停滞在G0/G1期和S期之间。此外,PZH处理和miR-34c-5p转染可下调细胞周期蛋白依赖性激酶4和cMyc(细胞增殖的促进因子)的表达,并增加p53(细胞凋亡的促进因子)的表达。这些结果表明,PZH可能通过上调miR-34c-5p的表达来抑制结直肠癌细胞的增殖,这为理解PZH的作用方式提供了新的视角。