Expression and significant roles of the long non-coding RNA CASC19/miR-491-5p/HMGA2 axis in the development of gastric cancer

BACKGROUND Gastric cancer(GC)is a common malignant tumor,long non-coding RNA and microRNA(miRNA)are important regulators that affect tumor proliferation,metastasis and chemotherapy resistance,and thus participate in tumor progression.CASC19 is a new bio-marker which can promote tumor invasion and metastasis.However,the mechanism by which CASC19 affects the progression of GC through miRNA is not clear.AIM To explore the role of the CASC19/miR-491-5p/HMGA2 regulatory axis in GC.METHODS To explore the expression and prognosis of CASC19 in GC through clinical samples,and investigate the effects of inhibiting CASC19 on the proliferation,migration,invasion and other functions of GC cells through cell counting Kit-8(CCK-8),ethynyldeoxyuridine,Wound healing assay,Transwell,Western blot and flow cytometry experiments.The effect of miR-491-5p and HMGA2 in GC were also proved.The regulatory relationship between CASC19 and miR-491-5p,miR-491-5p and HMGA2 were validated through Dual-luciferase reporter gene assay and reverse transcription PCR.Then CCK-8,Transwell,Wound healing assay,flow cytometry and animal experiments verify the role of CASC19/miR-491-5p/HMGA2 regulatory axis.RESULTS The expression level of CASC19 is related to the T stage,N stage,and tumor size of patients.Knockdown of the expression of CASC19 can inhibit the ability of proliferation,migration,invasion and EMT conversion of GC cells,and knocking down the expression of CASC19 can promote the apoptosis of GC cells.Increasing the expression of miR-491-5p can inhibit the proliferation of GC cells,miR-491-5p mimics can inhibit EMT conversion,and promote the apoptosis of GC cells,while decreasing the expression of miR-491-5p can promote the proliferation and EMT conversion and inhibit the apoptosis of GC cells.The expression of HMGA2 in GC tissues is higher than that in adjacent tissues.At the same time,the expression level of HMGA2 is related to the N and T stages of the patients.Reducing the level of HMGA2 can promote cell apoptosis and inhibit the proliferation of GC cells.Cell experiments and animal experiments have proved that CASC19 can regulates the expression of HMGA2 through miR-491-5p,thereby affecting the biological functions of GC.CONCLUSION CASC19 regulates the expression of HMGA2 through miR-491-5p to affect the development of GC.This axis may serve as a potential biomarker and therapeutic target of GC.

Effects of long non-coding RNA Opa-interacting protein 5 antisense RNA 1 on colon cancer cell resistance to oxaliplatin and its regulation of micro RNA-137

BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.

Long non-coding RNA MEG3 regulates autophagy after cerebral ischemia/reperfusion injury

Severe cerebral ischemia/reperfusion injury has been shown to induce high-level autophagy and neuronal death.Therefore,it is extremely important to search for a target that inhibits autophagy activation.Long non-coding RNA MEG3 participates in autophagy.However,it remains unclear whether it can be targeted to regulate cerebral ischemia/reperfusion injury.Our results revealed that in oxygen and glucose deprivation/reoxygenation-treated HT22 cells,MEG3 expression was obviously upregulated,and autophagy was increased,while knockdown of MEG3 expression greatly reduced autophagy.Furthermore,MEG3 bound mi R-181 c-5 p and inhibited its expression,while mi R-181 c-5 p bound to autophagy-related gene ATG7 and inhibited its expression.Further experiments revealed that mir-181 c-5 p overexpression reversed the effect of MEG3 on autophagy and ATG7 expression in HT22 cells subjected to oxygen and glucose deprivation/reoxygenation.In vivo experiments revealed that MEG3 knockdown suppressed autophagy,infarct volume and behavioral deficits in cerebral ischemia/reperfusion mice.These findings suggest that MEG3 knockdown inhibited autophagy and alleviated cerebral ischemia/reperfusion injury through the mi R-181 c-5 p/ATG7 signaling pathway.Therefore,MEG3 can be considered as an intervention target for the treatment of cerebral ischemia/reperfusion injury.This study was approved by the Animal Ethics Committee of the First Affiliated Hospital of Zhengzhou University,China(approval No.XF20190538)on January 4,2019.

Expressions of Long Non-Coding RNAs in Carcinogenesis of Cervix: A Review

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.

A polymorphism in GAS5 promoter impacts efficacy of cytarabine-based chemotherapy in Chinese AML patients

OBJECTIVE SNPs in lnc RNAs may alter the expression or secondary structure of lnc RNAs and then impact their functions.Whether lnc RNA SNPs affect the prognosis of acute myeloid leukemia(AML)remains unknown.To search the association between lnc RNA SNPs and AML outcomes,thirty tag SNPs in GAS5,H19,MALAT1,WT1-as and SRA were genotyped in313 AML patients.METHODS Survival analysis was performed in both AML patients recruited presently and GEO samples.The expression of GAS5 and TP63 was analyzed by real-time quantitative PCR.Dual-luciferase reporter gene assay was used to confirm the interactions between GAS5 rs55829688 and TP63.RESULTS Survival analysis indicated that rs55829688(T>C),located in GAS5 promoter,was significantly associated with the prognosis of AML.The average overall survival(OS)for patients with the rs55829688 CC genotype was significantly shorter than those carrying the rs55829688 T allele(P=0.018).Patients with rs55829688 CC genotype showed higher GAS5 expression in PBMCs than carriers of rs55829688T allele(P=0.025).Rs55829688 CC homozygotes also harbored a longer platelets recovery than those with rs55829688 T allele(P=0.040).In vitro study showed that GAS5 promoter harboring the rs55829688 C al ele showed marginal y increased reporter gene activity(P=0.054),and the promoter activity was increased by TP63 in a dose-dependent manner(P=0.001).Moreover,GAS5 expression was associated with AML OS in the GEO GSE12417 dataset,and GAS5 higher expression predict shorter OS(P=0.011).CONCLUSION Rs55829688 polymorphism could increase GAS5 expression by interacting with TP63 and was associated with worse OS in Chinese AML patients.

Expression Profile and Function Analysis of Long Non-coding RNAs in the Infection of Coxsackievirus B3

The roles of lnc RNAs in the infection of enteroviruses have been barely demonstrated. In this study, we used coxsackievirus B3(CVB3), a typical enterovirus, as a model to investigate the expression profiles and functional roles of lnc RNAs in enterovirus infection. We profiled lnc RNAs and m RNA expression in CVB3-infected He La cells by lnc RNA-m RNA integrated microarrays. As a result, 700 differentially expressed lnc RNAs(431 up-regulated and 269 down-regulated) and665 differentially expressed m RNAs(299 up-regulated and 366 down-regulated) were identified in CVB3 infection. Then we performed lnc RNA-m RNA integrated pathway analysis to identify potential functional impacts of the differentially expressed m RNAs, in which lnc RNA-m RNA correlation network was built. According to lnc RNA-m RNA correlation, we found that XLOC-001188, an lnc RNA down-regulated in CVB3 infection, was negatively correlated with NFAT5 m RNA,an anti-CVB3 gene reported previously. This interaction was supported by q PCR detection following si RNA-mediated knockdown of XLOC-001188, which showed an increase of NFAT5 m RNA and a reduction of CVB3 genomic RNA. In addition, we observed that four most significantly altered lnc RNAs, SNHG11, RP11-145 F16.2, RP11-1023 L17.1 and RP11-1021 N1.2 share several common correlated genes critical for CVB3 infection, such as BRE and IRF2 BP1. In all, our studies reveal the alteration of lnc RNA expression in CVB3 infection and its potential influence on CVB3 replication,providing useful information for future studies of enterovirus infection.

LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors

In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.