Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.
Pulmonary fibrosis is a kind of chronic and fibrotic lung disease caused by a variety of reasons, and its main pathological characteristic is excessive scar formation after the destruction of normal lung tissue structure, which eventually leads to respiratory insufficiency. Although the research on the pathophysiological mechanism of pulmonary fibrosis has made great progress, its pathogenesis has not been fully elucidated, and it is still clinically incurable. In recent years, studies have shown that non-coding RNAs are involved in the pathogenesis of pulmonary fibrosis, therefore, this article summarizes the related research progress of non-coding RNA in regulation of pulmonary fibrosis by affecting epithelial-mesenchymal transition, fibroblast activation and function of macrophages, in order to provide new ideas for the treatment of pulmonary fibrosis.
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.
Objective The aim of this study is to review the association between long non-coding RNA (lncRNA) and papillary thyroid carcinoma (PTC). Method The relevant literatures about lncRNA associated with PTC were retrospectively analyzed and summarized. Results The expression levels of noncoding RNA associated with MAP kinase pathway and growth arrest (NAMA), PTC susceptibility candidate 3 (PTCSC3), BRAF activated non-coding RNA (BANCR), maternally expressed gene 3 (MEG3), NONHSAT037832, and GAS8-AS1 in PTC tissues were significantly lower than those in non-thyroid carcinoma tissues. The expression levels of ENST00000537266, ENST00000426615, XLOC051122, XLOC006074, HOX transcript antisense RNA (HOTAIR), antisense noncoding RNA in the INK4 locus (ANRIL), and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PTC tissues were upregulated in PTC tissues, comparing with the non-thyroid carcinoma tissues. These lncRNAs were possibly involved in cell proliferation, migration, and apoptosis of PTC. Conclusion LncRNAs may provide new insights into the molecular mechanism and gene-targeted therapy of PTC and become new molecular marker for the diagnosis of PTC.
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.
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 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.
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.
ObjectivesTo systematically review the association between the expression level of LncRNA and clinicopathological features and prognostic value of gastric cancer.MethodsWe searched PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, VIP, WanFang Data and CBM databases to collect studies on the association between LncRNA overexpression and prognosis for gastric cancer from inception to April 2017. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 12.0 software.ResultsA total of 21 case-control studies were included. The results of meta-analysis showed that: LncRNA overexpression patients had poor TNM stage (OR=0.29, 95%CI 0.24 to 0.35, P<0.001), deeper tumor invasion (OR=0.24, 95%CI 0.12 to 0.49,P<0.001), shorter overall survival (OS) (HR=2.52, 95%CI 2.07 to 3.06,P<0.001) and disease-free survival (DFS) (HR=2.31, 95%CI 1.75 to 3.05,P<0.001).ConclusionsLncRNA overexpression is a poor prognosis risk factor for gastric cancer patients. Due to limited quantity and quality of the included studies, more high quality studies are needed to verify above conclusions.
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.