ABSTRACT
Objective:To observe the effect of Jianpi Xiaoai prescription on long non-coding RNA Hox transcript antisense intergenic RNA （lncRNA HOTAIR）/Janus kinase 2 （JAK2） /signal transducer and activator of transcription 3 （STAT3） signaling pathway and to explore the potential mechanism of Jianpi Xiaoai prescription in suppressing the metastasis of colon cancer. Method:The expression of lncRNA HOTAIR in different cells was analyzed. Following the treatment of HCT116 cells with 10%，15%，and 20% Jianpi Xiaoai prescription -containing serum， the invasive ability of Jianpi Xiaoai prescription on HCT116 cells was assessed by transwell assay. The mRNA expression levels of lncRNA HOTAIR，JAK2，and STAT3 were measured by Real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of JAK2， phosphorylated STAT3 （p-STAT3） and STAT3 by Western blot. Result:The highest expression of lncRNA HOTAIR was detected in HCT116 cells. Compared with the blank group， each Jianpi Xiaoai prescription group exhibited a decreased number of invasive cells （<italic>P</italic><0.05， <italic>P</italic><0.01）. The relative JAK2 mRNA expression in the middle-dose Jianpi Xiaoai prescription group was down-regulated （<italic>P</italic><0.05）， and the relative lncRNA HOTAIR mRNA expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative JAK2 mRNA expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （<italic>P</italic><0.01）. Compared with the blank group，the relative p-STAT3 protein expression was down-regulated in the middle-dose Jianpi Xiaoai prescription group （<italic>P</italic><0.05）， and the relative JAK2 protein expression in the middle- and high-dose Jianpi Xiaoai prescription groups and the relative p-STAT3 protein expression in the high-dose Jianpi Xiaoai prescription group were remarkably down-regulated （<italic>P</italic><0.01）. Conclusion:Jianpi Xiaoai prescription effectively inhibits the metastasis of colon cancer cells， which may be related to the inhibition of lncRNA HOTAIR/JAK2/STAT3 signaling pathway.
ABSTRACT
Several recent investigations show that HOX transcript antisense intergenic RNA (HOTAIR) play an important role in the pathogenesis of different cancers. HOTAIR polymorphisms has been widely studied in the context of association between with the risk of cancer pathogenesis. However, there is no certain conclusion about the role of HOTAIR polymorphisms in different cancer initiation and progression. Our team has selected eligible studies up to 1 May 2019, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. We have included total number of 102 case–control investigations extracted from 41 eligible articles for the current meta-analysis. We calculated pooled odds ratio (ORs) with their corresponding 95% confidence intervals (CIs) using either fixed-effect or random-effect models for quantitative evaluation of the strength for the association between HOTAIR gene polymorphisms and the risk of cancer. Our current meta-analysis investigation showed that HOTAIR rs4759314 polymorphism particularly increased the overall risk of cancer in different models including homozygous, recessive and allele genetic. HOTAIR rs920778 significantly raised the cancer risk only in recessive genetic model. HOTAIR rs12826786 polymorphism was associated with cancer development in heterozygous, homozygous, dominant, recessive and allele genetic models. Also, an increase in cancer risk was observed with rs874945 polymorphism of HOTAIR gene in heterozygous, dominant and allele genetic models. The rs12427129 polymorphism showed correlation with cancer susceptibility only in recessive model. Subgroup analysis based on cancer type suggested that rs4759314 polymorphism significantly increased the risk of gastric and cervical cancers, and the rs920778 polymorphism increased the risk of gastrointestinal, cervical and gastric cancers. In summary, this study found that HOTAIR polymorphisms are significantly associated with cancer development
ABSTRACT
BACKGROUND: A long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) is involved in epigenetic regulation through chromatin remodeling by recruiting polycomb repressive complex 2 (PRC2) proteins (EZH2, SUZ12, and EED) that induce histone H3 trimethylation at lysine 27 (H3K27me3). Deregulation of c-MYC and interaction between c-MYC and EZH2 are well known in lymphomagenesis; however, little is known about the expression status of HOTAIR in diffuse large B-cell lymphomas (DLBCLs). METHODS: The expression status of PRC2 (EZH2, SUZ12, and EED), H3K27me3, c-MYC, and BCL2 was analyzed using immunohistochemistry (n = 231), and HOTAIR was investigated by a quantification real-time polymerase chain reaction method (n = 164) in DLBCLs. RESULTS: The present study confirmed the positive correlation among PRC2 proteins, H3K27me3, and c-MYC in DLBCLs. Expression level of HOTAIR was also positively correlated to EZH2 (p < .05, respectively). Between c-MYC and HOTAIR, and between c- MYC/BCL2 co-expression and HOTAIR, however, negative correlation was observed in DLBCLs (p < .05, respectively). High level of H3K27me3 was determined as an independent prognostic marker in poor overall survival (hazard ratio, 2.0; p = .023) of DLBCL patients. High expression of HOTAIR, however, was associated with favorable overall survival (p = .004) in the univariate analysis, but the impact was not significant in the multivariate analysis. The favorable outcome of DLBCL with HOTAIR high expression levels may be related to the negative correlation with c- MYC expression or c-MYC/BCL2 co-expression. CONCLUSIONS: HOTAIR expression could be one of possible mechanisms for inducing H3K27me3 via EZH2-related PRC2 activation, and induced H3K27me3 may be strongly related to aggressive DLBCLs which show poor patient outcome.