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.
ObjectiveTo investigate the regulatory effect of long chain non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) adsorbing microRNA-124 (miR-124) on osteogenic differentiation of mesenchymal stem cells (MSCs).MethodsC3H10T1/2 cells derived from mouse embryos were cultured in vitro, then randomly divided into control group (group A), lncRNA MALAT1 no-load plasmid group (group B), lncRNA MALAT1 overexpression plasmid group (group C), lncRNA MALAT1 small interfering RNA (siRNA) group (group D), and lncRNA MALAT1 siRNA negative control group (group E). The cells were transfected into plasmids and siRNA, then induced to differentiate into osteoblasts. Alkaline phosphatase (ALP) and alizarin red staining were used to detect the osteogenic differentiation of cells in each group, real-time fluorescence quantitative (qRT-PCR) analysis was used to detect the expressions of lncRNA MALAT, miR-124, and osteogenesis-related genes such as Runt-related transcription factor 2 (Runx2), osteopontin (OPN), and osteocalcin (OCN) in each group. Double luciferase reporter gene was used to detect the targeting regulation of lncRNA MALAT1 to miR-124.ResultsThe relative contents of ALP positive cells, mineralized nodule, and the relative mRNA expressions of lncRNA MALAT1, Runx2, OPN, and OCN in group C were significantly higher than those in other groups (P<0.05), while in group D significantly lower than in other groups (P<0.05); the relative expression of miR-124 in group C was significantly lower than that in other groups(P<0.05), while in group D significantly higher than in other groups (P<0.05). There was no significant difference in these indexes between groups A, B, and E (P>0.05). The results of double luciferase reporter gene assay showed that lncRNA MALAT1 targeting down-regulated the expression of miR-124.ConclusionLncRNA MALAT1 can targeting down-regulate the expression of miR-124 and promote the osteogenic differentiation of MSCs.
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.
Aortic dissection is a catastrophic emergency with a high mortality rate, and its full pathogenesis remains unknown to researchers, which brings a heavy burden to the individuals, society and family because of its poor prognosis. Improving the efficiency of its diagnosis and treatment and defining the pathogenic mechanism clearly is a research hotspot. Recently, utilizing bioinformatics to find diagnostic biomarker of aortic dissection has attracted the attention of many researchers. Besides, exploring the relationship between pathogenic mechanism and inflammatory process, extracellular matrix degradation, elastic fiber fracture and the phenotypic transformation of vascular smooth muscle cells is also a hot topic. We summarize recent progress made in the pathogenesis of aortic dissection. We hope to identify key molecules driving aortic dissection and provide reliable reference for the diagnosis, medical treatment and prevention of aortic dissection.
Objective To investigate the expression and clinical value of long chain non-coding RNA nicotinamide nucleotide hydrogenase antisense RNA1 (LncRNA NNT-AS1), motor neuron and pancreas homeobox protein 1 antisense RNA1 (MNX1-AS1) in lung cancer patients. Methods This study selected 128 patients diagnosed with lung cancer admitted to The Third Medical Center of the General Hospital of the People’s Liberation Army from April 2020 to April 2021 as a cancer group. During the same period, 128 patients with benign pulmonary nodules were regarded as a benign group, and 128 healthy individuals who underwent physical examination were selected as a control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the levels of LncRNA NNT-AS1 and MNX1-AS1 in serum. A three-year follow-up was conducted on all lung cancer patients, with 52 patients in the death group and 76 patients in the survival group. Receiver operator characteristic (ROC) curve was applied to analyze the diagnostic value of serum LncRNA NNT-AS1 and MNX1-AS1 for the occurrence of lung cancer and their predictive value for prognosis. Results Compared with the control group, the serum levels of LncRNA NNT-AS1 and MNX1-AS1 were obviously increased in the benign group and the cancer group (P<0.05). Compared with the benign group, the levels of LncRNA NNT-AS1 and MNX1-AS1 in serum of the cancer patients were obviously increased (P<0.05). The area under ROC curve (AUC) of serum LncRNA NNT-AS1 combined with MNX1-AS1 for the diagnosis of lung cancer was higher than that of LncRNA NNT-AS1 and MNX1-AS1 alone (ZLncRNA NNT-AS1~LncRNA NNT-AS1+MNX1-AS1=2.496, P=0.013; ZMNX1-AS1~LncRNA NNT-AS1+MNX1-AS1=2.831, P=0.007). The levels of LncRNA NNT-AS1 and MNX1-AS1 were related to tumor differentiation, clinical stage, and lymph node metastasis (P<0.05). Compared with the survival group, the serum levels of LncRNA NNT-AS1 and MNX1-AS1 in the death group were obviously increased (P<0.05). The AUC of combined prediction for lung cancer prognosis by serum LncRNA NNT-AS1 and MNX1-AS1 was higher than that predicted by LncRNA NNT-AS1 and MNX1-AS1 alone (ZLncRNA NNT-AS1~LncRNA NNT-AS1+MNX1-AS1=2.539, P=0.011; ZMNX1-AS1~LncRNA NNT-AS1+MNX1-AS1=3.377, P=0.001). Conclusion LncRNA NNT-AS1 and MNX1-AS1 are highly expressed in serum of lung cancer patients, and both have certain value in diagnosis and prognosis evaluation of lung cancer.
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 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.
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.
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 molecular mechanisms and clinical treatment of gastric cancer with liver metastasis (GCLM), in order to provide new ideas for future treatment. MethodThe literatures about mechanism and treatment strategy of GCLM in recent years were searched and reviewed. ResultsMost patients with gastric cancer were in advanced stage or had developed distant metastases when they were first diagnosed, among which liver was the common site of metastasis. The complex molecular mechanisms of GCLM had not been fully clarified. Molecular mechanisms at different levels, including non-coding RNA, circulating tumor cells, exosomes, tumor microenvironment and signaling pathways, were relatively independent and interacted with each other, providing potential biomarkers and therapeutic targets for GCLM. At present, the best treatment method for patients with GCLM was mainly divided into local and systemic treatment. The local treatment included surgical treatment, radiofrequency ablation and proton beam therapy, while the systemic treatment included systemic chemotherapy, targeted therapy and immunotherapy, among which the targeted therapy and immunotherapy were the focus of recent research. ConclusionsThe mechanism of GCLM is the result of the interaction between tumor cells and the microenvironment at the site of metastasis. Understanding them is of great significance to guide clinical treatment and prognosis. At present, there is no unified treatment standard for GCLM. To achieve the ideal treatment effect, we should not only rely on single therapy, but also adopt multi-disciplinary and individual therapy according to the specific disease status of patients and the nature of tumors.