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 investigate the expression of growth arrest-specific 5 (GAS5) mRNA and its clinical significance in hepatocellular carcinoma.MethodsThe expression of GAS5 mRNA in the hepatocellular carcinoma tissues and corresponding adjacent tissues were detected by real time-PCR. The relationship between the expression of GAS5 mRNA and clinicopathological characteristics were analyzed by SPSS 19.0 software.ResultsThe expression of GAS5 mRNA in hepatocellular carcinoma tissues was significantly lower than that of the adjacent tissues (P<0.01). The expression of GAS5 mRNA was related to tumor size, tumor number, lymph node metastasis, clinical TNM stage, alpha fetoprotein level, and tumor differentiation (P<0.05). Cox hazard model results showed that low expression of GAS5 mRNA was associated with poor prognosis (P<0.05).ConclusionGAS5 mRNA is expected to be a diagnostic and prognostic marker for patients with hepatocellular carcinoma.
ObjectiveTo summarize the regulatory role of long non-coding RNA (lncRNA) in peripheral nerve injury (PNI) and neural regeneration.MethodsThe characteristics and mechanisms of lncRNA were summarized and its regulatory role in PNI and neural regeneration were elaborated by referring to relevant domestic and foreign literature in recent years.ResultsNeuropathic pain and denervated muscle atrophy are common complications of PNI, affecting patients’ quality of life. Numerous lncRNAs are upregulated after PNI, which promote the progress of neuropathic pain by regulating nerve excitability and neuroinflammation. Several lncRNAs are found to promote the progress of denervated muscle atrophy. Importantly, peripheral nerve regeneration occurs after PNI. LncRNAs promote peripheral nerve regeneration through promoting neuronal axonal outgrowth and the proliferation and migration of Schwann cells.ConclusionAt present, the research on lncRNA regulating PNI and neural regeneration is still in its infancy. The specific mechanism remains to be further explored. How to achieve clinical translation of experimental results is also a major challenge for future research.
Objective To investigate the role of long non-coding RNA metastasis-associated in colon cancer 1-antisense RNA （MACC1-AS1）in cisplatin resistant gastric cancer and its possible mechanism. Methods Human gastric cancer cell line BGC823 and cisplatin resistant gastric cancer cell line (BGC823/DDP) were selected as the research objects. BGC823/DDP cells were transfected and divided into negative control group (si-NC group, transfected with si-NC empty plasmid) and MACC1-AS1 gene silencing group (si-MACC1-AS1 group, transfected with si-MACC1-AS1 plasmid). The BGC823 cells were transfected and divided into positive control group (pcDNA-NC group, transfected with pcDNA-NC empty plasmid) and MACC1-AS1 gene overexpression group (pcDNA-MACC1-AS1 group, transfected with pcDNA-MACC1-AS1 plasmid). MTT was used to detect the inhibition and 50% inhibition concentration (IC50). Flow cytometry was used to detect apoptosis. Real-time fluorescence quantitative PCR was used to detect the mRNA expression levels of MACC1-AS1, B-lymphoma-2 gene (Bcl-2), Bcl-2 related X gene (Bax), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), protein kinase B (AKT), and phosphorylated AKT (p-AKT). Western blot was used to detect the protein expression levels of Bax, Bcl-2, p-mTOR, mTOR, AKT, and p-AKT. Results The relative expression level of MACC1-AS1 mRNA in BGC823/DDP cells was higher than that in BGC823 gastric cancer cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the si-MACC1-AS1 group cells was lower than that in the si-NC group cells (P<0.01). The relative expression level of MACC1-AS1 mRNA in the pcDNA-MACC1-AS1 group cells was higher than that in the pcDNA-NC group cells (P<0.01). The cell growth inhibition rate and IC50 of the si-MACC1-AS1 group were higher than those of the si-NC group (P<0.01). The cell growth inhibition rate and IC50 of the pcDNA-MACC1-AS1 group were lower than those of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the pcDNA-MACC1-AS1 group were significantly higher than those in the pcDNA-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the pcDNA-MACC1-AS1 group were significantly lower than those in the pcDNA-NC group (P<0.01). The apoptosis rate of the pcDNA-MACC1-AS1 group was significantly lower than that of the pcDNA-NC group (P<0.01). The mRNA and protein relative expression levels of Bcl-2, p-AKT/AKT and p-mTOR/mTOR in the si-MACC1-AS1 group were significantly lower than those in the si-NC group (P<0.01). The relative expression levels of Bax protein and mRNA in the si-MACC1-AS1 group were significantly higher than those in the si-NC group (P<0.01). The apoptosis rate of the si-MACC1-AS1 group was significantly higher than that of the si-NC group (P<0.01). Conclusions MACC1-AS1 highly expresses in cisplatin resistant gastric cancer cells. Overexpression of MACC1-AS1 regulates AKT/mTOR pathway mediated apoptosis and enhances cisplatin resistance of gastric cancer cells.
ObjectiveTo screen long non-coding RNAs (lncRNAs) relevant to programmed cell death (PCD) and construct a nomogram model predicting prognosis of hepatocellular carcinoma (HCC). MethodsThe HCC patients selected from The Cancer Genome Atlas (TCGA) were randomly divided into training set and validation set according to 1∶1 sampling. The lncRNAs relevant to PCD were screened by Pearson correlation analysis, and which associated with overall survival in the training set were screened by univariate Cox proportional hazards regression (abbreviation as “Cox regression”), and then multivariate Cox regression was further used to analyze the prognostic risk factors of HCC patients, and the risk score function model was constructed. According to the median risk score of HCC patients in the training set, the HCC patients in each set were assigned into a high-risk and low-risk, and then the Kaplan-Meier method was used to draw the overall survival curve, and the log-rank test was used to compare the survival between the HCC patients with high-risk and low-risk. At the same time, the area under receiver operating characteristic curve (AUC) was used to evaluate the value of the risk score function model in predicting the 1-, 3-, and 5-year overall survival rates of HCC patients in the training set, validation set, and integral set. Then the nomogram was constructed based on the risk score function model and factors validated in clinic, and its predictive ability for the prognosis of HCC patients was evaluated. ResultsA total of 374 patients with HCC were downloaded from the TCGA, of which 342 had complete clinicopathologic data, including 171 in the training set and 171 in the validation set. Finally, 8 lncRNAs genes relevant to prognosis (AC099850.3, LINC00942, AC040970.1, AC022613.1, AC009403.1, AL355974.2, AC015908.3, AC009283.1) were screened out, and the prognostic risk score function model was established as follows: prognostic risk score=exp1×β1+exp2×β2...+expi×βi (expi was the expression level of target lncRNA, βi was the coefficient of multivariate Cox regression analysis of target lncRNA). According to this prognostic risk score function model, the median risk score was 0.89 in the training set. The patients with low-risk and high-risk were 86 and 85, 86 and 85, 172 and 170 in the training set, validation set, and integral set, respectively. The overall survival curves of HCC patients with low-risk drawn by Kaplan-Meier method were better than those of the HCC patients with high-risk in the training set, validation set, and integral set (P<0.001). The AUCs of the prognostic risk score function model for predicting the 1-, 3-, and 5-year overall survival rates in the training set were 0.814, 0.768, and 0.811, respectively, in the validation set were 0.799, 0.684, and 0.748, respectively, and in the integral set were 0.807, 0.732, and 0.784, respectively. The multivariate Cox regression analysis showed that the prognostic risk score function model was a risk factor affecting the overall survival of patients with HCC [<0.89 points as a reference, RR=1.217, 95%CI (1.151, 1.286), P<0.001]. The AUC (95%CI) of the prognostic risk score function model for predicting the overall survival rate of HCC patients was 0.822 (0.796, 0.873). The AUCs of the nomogram constructed by the prognostic risk score function model in combination with clinicopathologic factors to predict the 1-, 3-, and 5-year overall survival rates were 0.843, 0.839, and 0.834. The calibration curves of the nomogram of 1-, 3-, and 5-year overall survival rates in the training set were close to ideal curve, suggesting that the predicted overall survival rate by the nomogram was more consistent with the actual overall survival rate. ConclusionThe prognostic risk score function model constructed by the lncRNAs relevant to PCD in this study may be a potential marker of prognosis of the patients with HCC, and the nomogram constructed by this model is more effective in predicting the prognosis (overall survival) of patients with HCC.
ObjectiveTo investigate relationship of long non-coding RNA FoxP4-AS1 expression with lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC).MethodsReal time fluorescent quantitative polymerase chain reaction was used to detect the expression level of FoxP4-AS1 in 52 cases of PTC tissues and corresponding adjacent tissues, PTC cells (TPC-1, B-CPAP, K1), and normal thyroid follicular epithelial cells (Nthy-ori3-1). Univariate and multivariate analysis were used to identify the influencing factors of LNM in PTC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of influencing factors of LNM in PTC.ResultsThe expression level of FoxP4-AS1 in the PTC tissues was significantly decreased as compared with the corresponding adjacent tissues (t=7.898, P<0.001), which in the different cells had statistical difference (F=29.866, P<0.001): expression levels in the TPC-1 and K1 cells were lower than Nthy-ori3-1 cells (P<0.05) and in the B-CPAP cells and Nthy-ori3-1 cells had no statistical difference (P>0.05) by multiple comparisons. Univariate analysis showed that the extraglandular invasion (χ2=4.205, P=0.040)and low expression of FoxP4-AS1 (χ2=7.144, P=0.008) were the influencing factors of LNM in PTC. Binary logistic regression analysis showed that extraglandular invasion [OR=9.455, 95%CI (1.120, 79.835), P=0.039] and low expression ofFoxP4-AS1[OR=5.437, 95%CI (1.488, 19.873), P=0.010] were risk factors for LNM of PTC. The area under the ROC curve ofFoxP4-AS1,extraglandular invasion alone, and combination of the two were 0.679, 0.656, and 0.785, respectively.ConclusionsFoxP4-AS1 is down-regulated in PTC. Low level of FoxP4-AS1 is a risk factor for LNM of PTC. Combined detection of expression level of FoxP4-AS1 and extraglandular invasion has a high predictive value for LNM of PTC.
Objective To explore relationship between long non-coding RNA maternally expressed gene 3 (MEG3) polymorphisms and risk of gastric cancer. Methods One hundred and seventy-two Han patients with gastric cancer (gastric cancer group) and 224 Han individuals for physical examination (control group) in the Yunnan Cancer Hospital from March 2013 to October 2017 were selected as subjects. The rs7158663 and rs4081134 polymorphisms of the MEG3 were genotyped by using a TaqMan technique. The associations between the 2 polymorphisms and the risk of the gastric cancer and its clinical features were analyzed using the SPSS software. Results The frequencies of the AG+AA genotype and the A allele of the MEG3 rs7158663 in the gastric cancer group were significantly higher than those in the control group using the GG genotype and G allele as a reference respectively ［adjusted OR=1.71, 95%CI (1.14, 2.56), P=0.010; adjusted OR=1.58, 95%CI (1.15, 2.19), P=0.005］ after the Chi-square test and the adjustment of age and gender. The frequencies of the AG+AA genotype and the A allele of the MEG3 rs4081134 had no significant differences between the gastric cancer group and the control group (P>0.017). Moreover, the polymorphisms of the MEG3 rs7158663 and rs4081134 were not associated with the clinical features of the gastric cancer (P>0.017). Conclusion MEG3 rs7158663 AG+AA genotype might be one of susceptibility gene of gastric cancer in Chinese Han population.
ObjectiveTo understand the research progress of related biomarkers in early diagnosis of gastric cancer in recent years.MethodThe domestic and foregin literatures on studies of biomarkers of early diagnosis of gastric cancer in recent years were reviewed.ResultsAt present, the sensitivity and specificity of serum tumor biomarkers of gastric cancer such as CEA and CA19-9 were lower, so the molecular markers that could predict, screen, and diagnose gastric cancer in the early stage were further explored. The recent studies suggested that microRNAs, long non-coding RNAs, circular RNAs, exosome, etc. molecular markers in early diagnosis of gastric cancer had better prospects of clinilal application.ConclusionWith the continuous development of molecular biology technology, the values of microRNAs, long non-coding RNAs, circular RNAs, DNA, etc. in early diagnosis of gastric cancer would be further explored.
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.
ObjectiveTo investigate the level of serum long non-coding RNA antisense non-coding RNA INK4 locus (LncRNA ANRIL) in patients with ulcerative colitis (UC), and to analyze the diagnostic value of serum LncRNA ANRIL level in UC. MethodsA total of 143 UC patients admitted to the First Affiliated Hospital of Henan University of Science and Technology from February 2015 to November 2019 were retrospectively analyzed, and 145 healthy people with normal physical examination in the First Affiliated Hospital of Henan University of Science and Technology were selected as the control group. The relationship between serum LncRNA ANRIL level and PCT/IL-17 level was analyzed, the serum levels of LncRNA ANRIL, PCT, and IL-17 were compared between the two groups, and their diagnostic value for UC was explored.ResultsThe disease degree of 143 UC patients: 41 cases were mild, 59 cases were moderate, and 43 cases were severe; endoscopic grade: 38 cases were grade Ⅰ, 65 cases were grade Ⅱ, and 40 cases were grade Ⅲ. Compared with the control group, the serum levels of LncRNA ANRIL, PCT, and IL-17 were increased in the UC group (P<0.05); the levels of serum LncRNA ANRIL, PCT, and IL-17 in the UC group increased gradually with the increase of disease severity and endoscopic grade (P<0.05). The serum levels of LncRNA ANRIL were positively correlated with the levels of PCT and IL-17 in the UC patients (r=0.596, P<0.001; r=0.492, P<0.001). The area under the curve (AUC) of serum LncRNA ANRIL level in the diagnosis of UC was 0.851, the cut-off value was 1.29, the sensitivity and specificity were 75.5% and 83.4%, respectively. The AUC of serum LncRNA ANRIL combined with PCT in the diagnosis of UC was 0.898, the corresponding sensitivity and specificity were 81.8% and 87.6%, respectively. The sensitivity and diagnostic value of combination of LncRNA ANRIL and PCT were higher than that of serum LncRNA ANRIL alone (Z=2.102, P=0.036). ConclusionsThe serum level of LncRNA ANRIL in UC patients is increased, which has a certain diagnostic value, and it combines with PCT can better predict UC.