Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis
Berberine Promotes Apoptosis of Colorectal Cancer via Regulation of the Long Non-Coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (CASC2)/AU-Binding Factor 1 (AUF1)/B-Cell CLL/Lymphoma 2 (Bcl-2) Axis
复制标题
DOI：
10.12659/msm.912082
复制
发表时间：
2019-01-25
影响因子：
3.1
通讯作者：
Wang, Xia
中科院分区：
文献类型：
--
作者：
Dai, Wei;Mu, Liyuan;Wang, Xia
背景：小檗碱是一种天然异喹啉生物碱，来源于小檗属植物，具有抗癌作用。虽然细胞行为可以通过长链非编码RNA（lncRNA）调节，但lncRNA在结肠直肠癌进展中的作用和小檗碱对结肠直肠癌的作用在很大程度上是未知的。材料/方法：采用逆转录-定量PCR（RT-qPCR）方法检测人大肠癌细胞中lncRNA、CASC 2和Bcl-2 mRNA的表达水平，并分析其在小檗碱治疗大肠癌过程中的作用。MTT法检测细胞活力。流式细胞术和TUNEL法检测癌细胞凋亡。RNA免疫沉淀（RIP）法检测lncRNA CASC 2与AUF 1、AUF 1与B细胞CLL/淋巴瘤2（Bcl-2）的相互作用。LncRNA CASC 2在小檗碱处理的细胞中上调，并且敲低LncRNA CASC 2逆转小檗碱诱导的细胞凋亡。此外，小檗碱处理和lncRNA CASC 2抑制抗凋亡基因Bcl-2，诱导促凋亡作用。结论：lncRNA CASC 2通过抑制Bcl-2的表达，介导小檗碱诱导的细胞凋亡。
Background: Berberine, a natural isoquinoline alkaloid derived from Berberis genus plants, has been reported to have anti-cancer effects. While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the contributions of lncRNAs in progression and berberine effects on colorectal cancer are largely unknown. Therefore, the present study investigated the involvement and regulatory function of lncRNA cancer susceptibility candidate 2 (CASC2) during the treatment of human colorectal cancer using berberine.Material/Methods: Reverse transcription-quantitative PCR (RT-qPCR) was performed to detect the expression levels of lncRNA CASC2 and Bcl-2 mRNA in colorectal cancer cells. MTT assay was performed to evaluate cell viability. Flow cytometry and TUNEL assay were used to analyze the apoptosis of cancer cells. RNA immunoprecipitation (RIP) assay was done to verify the interaction between lncRNA CASC2 and (AU-binding factor 1) AUF1, or AUF1 and B-cell CLL/lymphoma 2 (Bcl-2).Results: Treatment with berberine suppressed cell viability of colorectal cancer by promoting apoptosis level. LncRNA CASC2 was upregulated in cells treated with berberine, and knockdown of lncRNA CASC2 reversed the berberine-induced apoptosis. In addition, anti-apoptotic gene Bcl-2 was suppressed by berberine treatment and lncRNA CASC2, inducing the pro-apoptotic effects. Moreover, lncRNA CASC2 binds to AUF1, which sequestered AUF1 from binding to Bcl-2 mRNA, thus inducing the inactivation of Bcl-2 translation.Conclusions: Our study reveals that lncRNA CASC2 mediates the berberine-induced pro-apoptotic effect via inhibition of Bcl-2 expression at the post-transcriptional level.