ABSTRACT
To illustrate the potential function of lncRNA SBF2-AS1 in the progression of colorectal cancer (CRC) and the molecular mechanism. The relative level of SBF2-AS1 in CRC tissues and cell lines was determined by qRT-PCR. Its level in CRC patients with different tumor stages and tumor sizes was examined. After the knockdown of SBF2-AS1, proliferative, invasive abilities and apoptotic rate of CRC cells were evaluated. The correlation between SBF2-AS1 and PTEN was analyzed in CRC tissues. Furthermore, the subcellular distribution of SBF2-AS1 was assessed. Through RIP and ChIP assay, the interaction between SBF2-AS1 and PTEN was identified. Finally, the involvement of PTEN in SBF2-AS1-mediated CRC progression was analyzed. SBF2-AS1 was upregulated in CRC tissues and cell lines. Its level remained higher in CRC with worse tumor stage and larger tumor size. Knockdown of SBF2-AS1 attenuated proliferative, invasive abilities, but induced apoptotic rate of SW480 and DLD1 cells. A negative correlation was identified between expression levels of SBF2-AS1 and PTEN in CRC tissues. PTEN level was negatively regulated by SBF2-AS1. Subcellular distribution analysis indicated that SBF2-AS1 was mainly expressed in the nucleus. Furthermore, the RIP assay proved the binding of SBF2-AS1 to EZH2 and SUZ12. Knockdown of SBF2-AS1 attenuated the recruitment ability of EZH2 to PTEN. Notably, inhibited proliferation by transfection of sh-SBF2-AS1 1# was partially reversed after co-transfection of sh-PTEN. LncRNA SBF2-AS1 is upregulated in CRC. Knocking down of lncRNA SBF2-AS1 inhibits proliferation, and invasion and induces apoptosis of colorectal cancer by interacting with EZH2 to downregulate PTEN level.
Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , MicroRNAs/genetics , Cell Line, Tumor , Neoplasm Invasiveness/genetics , Apoptosis/genetics , Cell Proliferation/genetics , Cell Movement/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolismABSTRACT
PURPOSE: ß-elemene has a wide range of anticancer effects and can be used in a variety of cancer types. This study mainly explored its mechanism of action on TNBC cells and provided theoretical basis for the treatment of TNBC. METHODS: Firstly, TNBC cells were treated with different concentrations of ß-elemene, and screened out an appropriate concentration for subsequent research. Then, through the bioinformatics website, predicted genes that have a binding relationship with ß-elemene. Then, the overexpression vector of the selected gene was transfected into the cell. The effects of ß-elemene and its target genes on the proliferation and apoptosis of TNBC cells were detected by CCK-8, Edu assay, and flow cytometry, and the senescence of cells was determined by SA-ß-gal experiment. Western blotting was used to detect the expression of apoptosis and aging-related proteins. RESULTS: ß-elemene inhibited TNBC cell viability and proliferation in a concentration-dependent manner, and induces apoptosis and senescence. Through the screening of candidate genes, IGF1 was finally determined to be an effective target gene of ß-elemene. The expression level of IGF1 was decreased in cells treated with ß-elemene. Overexpression of IGF1 significantly alleviated ability of ß-elemene to inhibit cell viability, proliferation, and induced cell apoptosis and senescence. In addition, ß-elemene inhibited the expression of IGF1R and Bcl-2, and promoted the expression of Cleaved Caspase-3 and senescence-related proteins (p27, p16, p53 and p21), and these effects were reversed by overexpression of IGF1. CONCLUSION: ß-elemene induced apoptosis and senescence of triple-negative breast cancer cells through IGF1/IGF1R pathway.
Subject(s)
Sesquiterpenes , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Cell Line, Tumor , Sesquiterpenes/pharmacology , Apoptosis , Cell Proliferation , Insulin-Like Growth Factor I , Receptor, IGF Type 1/pharmacologyABSTRACT
PURPOSE: To evaluate the effect of combination maintenance therapy of pemetrexed plus bevacizumab for patients with advanced non-small cell lung cancer. METHODS: We identified relevant studies by electronic search (Embase, PubMed, Cochrane, and Web of Science from 1 January 1960 to 29 October 2016) and manual search. The primary outcome of interest was progression-free survival (PFS) and secondary end point included overall survival (OS) and toxicities. The data was pooled for quantitative analysis and the final effect size was reported as hazard ratio (HR) for survival outcomes and relative risk (RR) for safety outcomes, both with a random-effects model. RESULTS: Three randomized controlled trials enrolling 1302 patients with advanced non-small cell lung cancer were included in this meta-analysis. An evident PFS improvement (HR = 0.73, 95% CI = 0.63-0.83, P < 0.01) was observed in patients with pemetrexed and bevacizumab combination maintenance therapy compared with single-agent maintenance therapy, yet it did not subsequently lead to a significant improvement in OS (HR = 0.97, 95% CI = 0.84-1.10, P = 0.66). Our analysis also showed statistically increased risks for provoking grade 3-4 adverse events in patients managed using pemetrexed plus bevacizumab combination (RR = 1.59, 95% CI = 1.07-2.36, P = 0.022). CONCLUSIONS: Pemetrexed plus bevacizumab combination maintenance therapy leads to significant improvement in PFS but not in OS for patients with advanced non-small cell lung cancer, which also increases the risks of grade 3-4 adverse events. Yet, in view of the limitation of existing studies and this meta-analysis, current evidence is not adequate to support routine use of pemetrexed-bevacizumab maintenance.
