ABSTRACT
Long noncoding RNA (lncRNA) are defined as noncoding RNA with a length of more than 200 nucleotides, which can regulate a variety of cellular processes. LncRNA H19 is widely involved in the pathophysiological process of intestinal inflammation and intestinal cancer by regulating the function of intestinal mucosal barrier. This article reviewed the effect of lncRNA H19 on intestinal mucosal barrier under different intestinal states and inflammation-cancer related signaling pathway.
ABSTRACT
Long noncoding RNA (lncRNA) H19, a well-known oncogenic lncRNA, is overexpressed in various cancers. Several studies have investigated the association between polymorphisms in lncRNA H19 and the risk of various cancer types; however, the findingswere inconsistent. In this study,we performed ameta-analysis to identify the precise association between H19 polymorphismsand cancer risk. Appropriate studies were retrieved from searching Web of Science, PubMed, Scopus, and Google scholar databases, updated 25 November 2018. The pooled odds ratios (ORs with 95% confidence intervals (CIs) were calculated to estimate the strength of the association between H19 polymorphisms and cancer risk. Our findings revealed that the H19-rs217727 C>T polymorphism is significantly associated with an increased risk of overall cancer in homozygous codominant (OR=1.28, 95%CI=1.04–1.57, P =0.020, TT vs CC), dominant (OR=1.20, 95% CI=1.04–1.37, P =0.010, CT+TT vs CC), recessive (OR=1.21, 95% CI=1.00–1.46, P =0.048, TT vs CT+CC), and allele (OR=1.16, 95%CI=1.05–1.28, P =0.003, T vs C) genetic models. No significant correlations were observed between H19: rs2839698 G>A, rs2107425 C>T, rs2735971 C>T, rs3024270 G>C, rs3741219 T>C, rs2839701 C>G, rs2735469 C>T, rs17658052 G>A, and rs3741216 T>A polymorphisms and overall cancer risk. Stratified analysis by cancer type proposed that the rs217727 variant is associated with increased risk of oral squamous cell carcinoma (OSCC) andlung cancer, whereas the rs2839698 variant is associated with increased risk of gastrointestinal cancer. Taken together, these findings support an association between H19 rs217727, and rs2839698 polymorphisms and cancer susceptibility. Larger and well-designed studies are necessary to further confirm these findings in detail.
ABSTRACT
AIM:To validate the association between long noncoding (lncRNA)-H19 and microRNA-199a-5p (miR-199a-5p) through the dual-luciferase reporter gene system by construction of a luciferase reporter vector containing the gene of lncRNA-H19.METHODS:The potential complementary binding sites of lncRNA-H19 and miR-199a-5p were predicted by RegRNA 2.0.The H19 gene or its mutant ( Mut) fragment was cloned into luciferase reporter vector psi-CHECK-2.Restriction enzyme analysis and sequence analysis were used to identify whether the recombinant plasmids of the H19 and H19-Mut were successfully constructed .miR-199a-5p mimics, miR-199a-5p inhibitor, miR-199a-5p mimics neg-ative control or miR-199a-5p inhibitor negative control was co-transfected into the 293T cells with the luciferase reporters containing H19 or H19-Mut.Dual-luciferase reporter assay was performed to detect the luciferase activity in different groups in order to verify the relationship between lncRNA-H19 and miR-199a-5p.RESULTS:The results of double enzyme diges-tion and DNA sequencing showed that the sequence of luciferase reporter vector was correct .The results of dual-luciferase reporter assay indicated that the H 19 reporter gene luciferase activity significantly decreased in miR-199a-5p mimics group by 49%(P<0.01), and the H19 reporter gene luciferase activity was obviously upregulated in miR-199a-5p inhibitor group compared with miR-199a-5p mimics group ( P<0.01).However, miR-199a-5p mimics, miR-199a-5p inhibitor, miR-199a-5p mimics negative control and miR-199a-5p inhibitor negative control showed no effect at H 19-Mut reporter gene.CONCLUSION:lncRNA-H19 binds to miR-199a-5p to exert an inhibitory effect at transcriptional level .
ABSTRACT
OBJECTIVE: To investigate the expression profile of long non-coding RNA H19 (LncRNA H19) in tamoxifen-resistant breast cancer cell lines, and to study its biological functions on cell invasion. METHODS: Quantitative reverse-transcription PCR(Q-PCR) was performed to detect the expression of LncRNA H19 in MCF-7W and MCF-7R cells. To further explore its biological function, RNA interference was applied. siRNA H19 was transfected to down-regulate H19 expression, and transfection efficiency was evaluated by Q-PCR. The epidermal mesenchymal transition-related transcription gene Snail 2 was also evaluated by Q-PCR. Transwell assay was performed to evaluate the effect of H19 expression on invasion potential of MCF-7R cells. RESULTS: Compared with MCF-7W cells, MCF-7R cells exhibit a relatively high expression of lncRNA H19 and Snail2. LncRNA H19 expression was down-regulated in MCF-7R after transfection of siRNA H19 for 24 h. Snail 2 mRNA expression was significantly inhibited after down regulating H19 expression (P<0.01). Transwell assay indicated that inhibition of LncRNA H19 by siRNA H19 could repress cell invasion (P<0.01). CONCLUSION: The expression of LncRNA H19 is significantly up-regulated in MCF-7R, and its downregulation attenuated the invasion behavior and related gene expression of tamoxifen-resistant breast cancer cell. H19 may be a drug treatment target of tamoxifen-resistant breast cancer metastasis.