Long non-coding RNA (lncRNA) Dnm3os plays a critical role in peritendinous fibrosis and pulmonary fibrosis, but its role in the process of cardiac fibrosis is still unclear. Therefore, we carried out study by using the myocardial fibrotic tissues obtained by thoracic aortic constriction (TAC) in an early study of our group, and the in vitro cardiac fibroblast activation model induced by transforming growth factor-β1 (TGF-β1). Quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and collagen gel contraction test were used to identify the changes of activation phenotype and the expression of Dnm3os in cardiac fibroblasts. Small interfering RNA was used to silence Dnm3os to explore its role in the activation of cardiac fibroblasts. The results showed that the expression of Dnm3os was increased significantly in myocardial fibrotic tissues and in the activated cardiac fibroblasts. And the activation of cardiac fibroblasts could be alleviated by Dnm3os silencing. Furthermore, the TGF-β1/Smad2/3 pathway was activated during the process of cardiac fibroblasts activation, while was inhibited after silencing Dnm3os. The results suggest that Dnm3os silencing may affect the process of cardiac fibroblast activation by inhibiting TGF-β1/Smad2/3 signal pathway. Therefore, interfering with the expression of lncRNA Dnm3os may be a potential target for the treatment of cardiac fibrosis.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
ObjectiveTo explore the differential expressed lncRNA genes associated with formation of cholesterol gallstone, and analyze the biological functions of differential expressed lncRNA through bioinformatics.MethodsA total of 24 C57BL/6 mice were randomly divided into normal control group (n=8) and lithogenic group (n=16), which were treated with chow diets and lithogenic diets respectively for 5 weeks. After 5 weeks, mice of the lithogenic group were randomly divided into model control group (n=8) and ursodeoxycholic acid treatment group (n=8). Afterwards, mice of the normal control group were still fed with chow diets, mice of the model control group were fed with lithogenic diets, mice of the ursodeoxycholic acid treatment group were fed with ursodeoxycholic acid. After 2 weeks, collected liver tissues and gallbladder bile from the three groups, and observed gallbladder gross sample and analyzed lipids component of gallbladder bile, meanwhile detected the differential expressed lncRNA and analyzed the biological functions of differential expressed lncRNA through bioinformatics, including Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.ResultsWe successfully constructed the mice model of cholesterol gallstone. Total cholesterol level of gallbladder in the model control group had significantly higher than those of the normal control group and ursodeoxycholic acid treatment group (P<0.05), yet there was no significant difference between the normal control group and ursodeoxycholic acid treatment group (P=0.59). The levels of total bile acid, total bilirubin, and direct bilirubin had no significant difference among the three groups (P>0.05). There were 49 kinds of common overlapped difference lncRNA between the ursodeoxycholic acid treatment group and the model control group through differential expression analysis of lncRNA in liver tissues of the mice in three groups. GO and KEGG path analysis were performed separately by differential expressed lncRNA, and 88 kinds of GO terms and 18 kinds of pathways were significantly enriched from the model control group and the normal control group, 205 kinds of GO terms and 20 kinds of pathways were significantly enriched from the ursodeoxycholic acid treatment group and the normal control group.ConclusionsUrsodeoxycholic acid has therapeutic effect for cholesterol gallstone. Differential expressed lncRNAs play an important regulatory role in the formation of cholesterol gallstone and the prevention of gallstone formation by ursodeoxycholic acid treatment, which further lay the foundation in discussing specific mechanism regulated by lncRNA.
ObjectiveTo understand advances in diagnostic value of long non-coding RNA (LncRNA) in hepatocellular carcinoma (HCC) and to find a useful tumor marker for early diagnosis of HCC.MethodThe recent literatures relevant the LncRNA in the HCC were reviewed and summarized.ResultsThe LncRNA could be detected in the blood and urine of the patients by the RNA immunoprecipitation, sequencing technology, gene chip, real-time quantitative PCR, and other techniques. With the rise of RNA sequencing technology, the number of identified LncRNAs had increased rapidly, and the remarkable progress had been made in the field of liver diseases. At present, the LncRNA related to HCC mainly included the urothelial cancer associated 1, highly up-regulated in liver cancer, metastasis-associated lung adenocarcinoma transcript 1, HOXA transcript at the distal tip, H19, SPRY4 intronic transcript 1, plasma-cytoma variant translocation gene 1, uc002mbe.2, uc007biz.1, etc., which were stable in the blood or urine and abnormally expressed in the HCC, alone or as a supplement to alpha-fetoprotein could obviously improve the sensitivity and specificity of diagnosis of HCC, even increased the sensitivity to 100%.ConclusionsLncRNA is specifically expressed in HCC and is expected to be a novel biomarker for early diagnosis of HCC. However, LncRNA has many types, diverse structures, and complex molecular regulation mechanisms. It is very difficult to find a strong combination or combinations to replace or supplement traditional biomarkers and to be clinically useful further efforts. It is believed that with deepening of LncRNA research in HCC, it will have a broader prospect in early screening, diagnosis, and prognosis of HCC.
ObjectiveTo investigate the expression level of long non-coding RNA Down’s syndrome critical region 8 (LncRNA DSCR8) in gastric cancer and its clinical significance.MethodsEighty-six patients with gastric cancer who were hospitalized in our hospital from August 2014 to August 2015 were selected as the research object. Real-time quantitative PCR (qRT-PCR) was used to detect the expression level of LncRNA DSCR8 mRNA in gastric cancer tissues and its adjacent tissues. The relationship between the expression level of LncRNA DSCR8 mRNA and clinicopathological features of gastric cancer was analyzed. Kaplan-Meier method was used to analyze the relationship between the expression of LncRNA DSCR8 mRNA and the survival rate of patients, and multivariate Cox proportional hazards regression analysis was used to analyze the prognostic factors of gastric cancer.ResultsThe expression level of LncRNA DSCR8 mRNA in gastric cancer tissues was higher than that in the paracancerous tissues (P<0.001). The expression levels of LncRNA DSCR8 mRNA in patients with poorly differentiated, TNM Ⅲ–Ⅳ and lymph node metastasis were higher than those in patients with well/moderately differentiated, TNM Ⅰ–Ⅱ and no lymph node metastasis (P<0.05). The 1, 3 and 5-year survival rate of patients with low LncRNA DSCR8 mRNA expression (97.62%, 92.86%, 83.33%, respectively) were higher than those of patients with high LncRNA DSCR8 mRNA expression (63.64%, 38.64%, 31.82%, respectively), P<0.05. LncRNA DSCR8 mRNA and TNM stage were independent risk factors of death in patients with gastric cancer (P<0.05).ConclusionsLncRNA DSCR8 is associated with the occurrence, development and prognosis of gastric cancer. It may be an important molecular marker of tumor stage and lymph node metastasis in patients with gastric cancer.
The pathogenesis of diabetic retinopathy (DR) is complex. Antisense non-coding RNA (ANRIL) in the INK4 locus in long-chain non-coding RNA (lncRNA) is closely related to cell proliferation, differentiation, and individual development. It plays an important role in the dysplasia of retinal vascular endothelial cells and is a new field in the study of the pathogenesis of DR. According to the researches at present, ANRIL may plays its role in the occurrence and development of DR through the signal pathway of nuclear factor-κB and ROS/polyadenylation diphosphate ribose polymerase, and interact with p300, miR-200b, and EZH2 to regulating the expression and function of VEGF. Specific blocking ANRIL and its related pathways may become a new target in the treatment of DR.
ObjectiveTo summarize the recent advances in the relationship between long non-coding RNA (LncRNA) and tumor autophagy, autophagy and drug resistance regulation.MethodsReviewed the relevant literatures at home and abroad, and reviewed the recent research progress of LncRNA regulation of autophagy to affect tumor resistance.ResultsDrug resistance was a common problem in the process of anti-tumor therapy. Autophagy played an important role in the process of tumor resistance as an important mechanism to maintain cell homeostasis. Abnormal regulation of LncRNA could contribute to the occurrence and development of tumors, and could also mediate the resistance of tumor cells to anti-tumor drugs by promoting or inhibiting autophagy.ConclusionsLncRNA can mediate tumor autophagy in a positive or negative direction, and autophagy is a " double-edged sword” for tumor resistance. LncRNA may improve tumor resistance to drugs by regulating autophagy.
Non-coding RNA (ncRNA) is a newly discovered functional RNA different from messenger RNA, which can participate in the regulation of tumor occurrence and development. Studies have shown that ncRNA can participate in the regulation of radiotherapy response to gastric cancer, and its mechanism may be related to its influence on DNA damage repair, gastric cancer cell stemness, apoptosis, and activation of epidermal growth factor receptor signal pathway. This article summarizes the mechanism of ncRNA regulating the response of gastric cancer to radiotherapy, and looks forward to the potential clinical application of ncRNA in the resistance of gastric cancer to radiotherapy.
Objective To investigate the effect of non-coding RNA activated by DNA damage (NORAD) on acute lung injury (ALI) in septic rats by regulating the miR-155-5p/TLR6 molecular axis. Methods The rats were randomly divided into control group, model group, low NORAD expression no-load group (LV-sh-NC), low NORAD expression group (LV-sh-NORAD), low NORAD expression +miR-155-5p low expression no-load group (LV-sh-NORAD+NC antagomir), NORAD low expression +miR-155-5p low expression group (LV-sh-NORAD+miR-155-5p antagomir). ELISA kits were applied to detect interleukin (IL)-8, IL-1β, and tumor necrosis factor-α (TNF-α) levels; quantitative real-time polymerase chain reaction was applied to detect the expression of NORAD, miR-155-5p, and Toll-like receptor 6 (TLR6) genes in lung tissue of rats in each group. The ratio of wet weight to dry weight (W/D) of lung tissue was measured. The pathological changes of lung tissue were observed by hematoxylin-eosin staining, and apoptosis in lung tissue cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Western blot was applied to detect the expressions of TLR6, Bax, Bcl-2, and cleaved cysteinyl aspartate specific proteinase 3 caspase-3) proteins in cells. Dual luciferase reporter gene experiment was applied to verify the relationship between miR-155-5p and NORAD and TLR6. Results Compared with the control group, the lung tissue of rats in the model group and LV-sh-NC group was obviously damaged, the levels of serum IL-1β, TNF-α, IL-8, expression of NORAD and TLR6 mRNA in lung tissue, W/D ratio, apoptosis rate, expression of TLR6, Bax, and Cleaved-caspase-3 proteins were obviously increased, the expression of miR-155-5p and Bcl-2 proteins in lung tissue was obviously reduced (P<0.05). Down-regulation of NORAD expression could reduce lung tissue injury, serum IL-1β, TNF-α, IL-8 levels, mRNA expression of NORAD and TLR6 in lung tissue, W/D ratio, apoptosis rate, TLR6, Bax, Cleaved caspase-3 protein expression, and cleaved caspase-3 protein expression. The expression of miR-155-5p and Bcl-2 protein in lung tissue were significantly increased (P<0.05). Down-regulating the expression of miR-155-5p could reduce the improvement effect of negatively regulated NORAD on sepsis ALI rats (P<0.05). Conclusion Interference with NORAD can alleviate lung injury in ALI rats by regulating the miR-155-5p/TLR6 molecular axis.
Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. MethodsDNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. ResultsThe expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.