Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Long noncoding RNA steroid receptor RNA activator 1 inhibits proliferation and glycolysis of esophageal squamous cell carcinoma

BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.

Long Non-coding RNA MEG3 Induces Renal Cell Carcinoma Cells Apoptosis by Activating the Mitochondrial Pathway

Summary： This study aimed to examine the effect of long non-coding RNA （LncRNA） MEG3 on the biological behaviors of renal cell carcinoma （RCC） cells 786-0 and the possible mechanism. MEG3 expression levels were detected by RT-qPCR in Rmaor tissues and adjacent non-tumor tissues from 29 RCC patients and in RCC lines 786-0 and SN12 and human embryonic kidney cell line 293T. Plasmids GV144-MEG3 （MEG3 overexpression plasmid） and GV144 （control plasmid） were stably transfected into 786-0 cells by using lipofectamine 2000. Cell viabilities were determined by MTT, cell apoptosis rates by flow cytometry following PE Annexin V and 7AAD staining, apoptosis-related protein expressions by Western blotting, and Bcl-2 mRNA by RT-qPCR in the transfected cells. The results showed that MEG3 was evidently downregulated in RCC tissues （P〈0.05） and RCC cell lines （P〈0.05）. The viabilities of 786-0 cells were decreased significantly after transfection with GV144-MEG3 for over 24 h （P〈0.05）. Consistently, the apoptosis rate was significantly increased in 786-0 cells transfected with GV144-MEG3 for 48 h （P〈0.05）. Furthermore, overexpression of MEG3 could reduce the expression of Bcl-2 and procaspase-9 proteins, enhance the expression of cleaved caspase-9 protein, and promote the release of cytochrome c protein to cytoplasm （P〈0.05）. Additionally, Bcl-2 mRNA level was declined by MEG3 overexpression （P〈0.05）. It was concluded that MEG3 induces the apoptosis of RCC cells possibly by activating the mitochondrial pathway.

Long non-coding RNAs in stem cells and cancer

An overwhelming majority of the transcribed genome encodes for non-coding RNA(ncR NA) sequences. Deep sequencing of the transcriptome has uncovered tens of thousands of long ncR NA(lncR NA) sequences. However, little is known regarding the possible functions for a vast majority of these sequences. Among those lncR NAs whose function has been experimentally validated, most serve as regulators of gene expression. LncR NAs have been found to be critical to development and homeostasis and they have been implicated in several pathologies including cancer. Here, we examine the functions and underlying mechanisms of lnc RNAs in stem cells and in cancer biology, areas linked by the actions of lncR NAs.

Long non-coding RNA NONMMUG014387 promotes Schwann cell proliferation after peripheral nerve injury

Schwann cells play a critical role in peripheral nerve regeneration through dedifferentiation and proliferation. In a previous study, we performed microarray analysis of the sciatic nerve after injury. Accordingly, we predicted that long non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after peripheral nerve injury, as bioinformatic analysis revealed that the target gene of NONMMUG014387 was collagen triple helix repeat containing 1（Cthrc1）. Cthrc1 may promote cell proliferation in a variety of cells by activating Wnt/PCP signaling. Nonetheless, bioinformatic analysis still needs to be verified by biological experiment. In this study, the candidate long non-coding RNA, NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus transfection. Plasmid p HBAd-MCMV-GFP-NONMMUG014387 and p HBAd-MCMV-GFP were transfected into Schwann cells. Schwann cells were divided into three groups： control（Schwann cells without intervention）, Ad-GFP（Schwann cells with GFP overexpression）, and Ad-NONMMUGO148387（Schwann cells with GFP and NONMMUGO148387 overexpression）. Cell Counting Kit-8 assay was used to evaluate proliferative capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase chain reaction and western blot assay were performed to investigate target genes and downstream pathways of NONMMUG014387. Cell proliferation was significantly increased in Schwann cells overexpressing lnc RNA NONMMUG014387 compared with the other two groups. Further, compared with the control group, m RNA and protein levels of Cthrc1, Wnt5 a, ROR2, Rho A, Rac1, JNK, and ROCK were visibly up-regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non-coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.

Value of long non-coding RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy

BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.

Long non-coding RNA: The functional regulator of mesenchymal stem cells

Mesenchymal stem cells(MSCs) are a subset of multipotent stroma cells residing in various tissues of the body. Apart from supporting the hematopoietic stem cell niche, MSCs possess strong immunoregulatory ability and multiple differentiation potentials. These powerful capacities allow the extensive application of MSCs in clinical practice as an effective treatment for diseases.Therefore, illuminating the functional mechanism of MSCs will help to improve their curative effect and promote their clinical use. Long noncoding RNA(LncRNA) is a novel class of noncoding RNA longer than 200 nt. Recently,multiple studies have demonstrated that LncRNA is widely involved in growth and development through controlling the fate of cells, including MSCs. In this review, we highlight the role of LncRNA in regulating the functions of MSCs and discuss their participation in the pathogenesis of diseases and clinical use in diagnosis and treatment.

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis,which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells(MSCs).Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases,including osteoporosis and osteoarthritis.In addition to conventional genetic modifications,epigenetic modifications(i.e.,DNA methylation,histone modifications,and the expression of noncoding RNAs)are considered to be contributing factors that affect bone homeostasis.Long noncoding RNAs(lncRNAs)were previously regarded as‘transcriptional noise’with no biological functions.However,substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases.In this review,we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

A novel long non-coding RNA NFIA-AS1 is down-regulated in gastric cancer and inhibits proliferation of gastric cancer cells

Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.

Granular Cell Tumor of the Esophagus: A Patient Treated by Endoscopic Mucosal Resection with Long Term Follow-Up

Granular cell tumors (GCTs) of the esophagus are uncommon. We report a case of granular cell tumor of esophagus treated by endoscopic mucosal resection (EMR) with long term follow-up.

Is mandible derived mesenchymal stromal cells superior in proliferation and regeneration to long bone-derived mesenchymal stromal cells?

Mesenchymal stromal cells(MSCs)are cells with the characteristic ability of self-renewal along with the ability to exhibit multilineage differentiation.Bone marrow(BM)is the first tissue in which MSCs were identified and BM-MSCs are most commonly used among various MSCs in clinical settings.MSCs can stimulate and promote osseous regeneration.Due to the difference in the development of long bones and craniofacial bones,the mandibular-derived MSCs(M-MSCs)have distinct differentiation characteristics as compared to that of long bones.Both mandibular and long bone-derived MSCs are positive for MSC-associated markers such as CD-73,-105,and-106,stage-specific embryonic antigen 4 and Octamer-4,and negative for hematopoietic markers such as CD-14.

Long-pulse gastric electrical stimulation protects interstitial cells of Cajal in diabetic rats via IGF-1 signaling pathway

AIM: To investigate the effects of different parameters of gastric electrical stimulation (GES) on interstitial cells of Cajal (ICCs) and changes in the insulin-like growth factor 1 (IGF-1) signal pathway in streptozotocin-induced diabetic rats. METHODS: Male rats were randomized into control, diabetic (DM), diabetic with sham GES (DM + SGES), diabetic with GES1 (5.5 cpm, 100 ms, 4 mA) (DM + GES1), diabetic with GES2 (5.5 cpm, 300 ms, 4 mA) (DM + GES2) and diabetic with GES3 (5.5 cpm, 550 ms, 2 mA) (DM + GES3) groups. The expression levels of c-kit, M-SCF and IGF-1 receptors were evaluated in the gastric antrum using Western blot analysis. The distribution of ICCs was observed using immunolabeling for c-kit, while smooth muscle cells and IGF-1 receptors were identified using alpha-SMA and IGF-1R antibodies. Serum level of IGF-1 was tested using enzyme-linked immunosorbent assay. RESULTS: Gastric emptying was delayed in the DM group but improved in all GES groups, especially in the GES2 group. The expression levels of c-kit, M-SCF and IGF-1R were decreased in the DM group but increased in all GES groups. More ICCs (c-kit(+)) and smooth muscle cells (alpha-SMA(+)/IGF-1R(+)) were observed in all GES groups than in the DM group. The average level of IGF-1 in the DM group was markedly decreased, but it was up-regulated in all GES groups, especially in the GES2 group. CONCLUSION: The results suggest that long-pulse GES promotes the regeneration of ICCs. The IGF-1 signaling pathway might be involved in the mechanism underlying this process, which results in improved gastric emptying.

Long-term survival of early-stage non-small cell lung cancer patients who underwent robotic procedure:a propensity score-matched study

Background:In the past decade,many researchers focused on to robot-assisted surgery.However,on long-term outcomes for patients with early-stage non-small cell lung cancer(NSCLC),whether the robotic procedure is superior to video-assisted thoracic surgery(VATS) and thoracotomy is unclear.Nonetheless,in the article titled "Long-term survival based on the surgical approach to lobectomy for clinical stage I non-small cell lung cancer:comparison of robotic,video assisted thoracic surgery,and thoracotomy lobectomy" by Yang et al.that was recently published in Annals of Surgery,the authors provided convincing evidence that the robotic procedure results in similar long-term survival as compared with VATS and thoracotomy.Minimally invasive procedures typically result in shorter lengths of hospital stay,and the robotic procedure in particular results in superior lymph node assessment.Main body:Our propensity score-matched study generated high-quality data.Based on our findings,we see promise in expanding patient access to robotic lung resections.In this study,propensity score matching minimized the bias involved between groups.Nevertheless,due to its retrospective nature,bias may still exist.Currently,the concept of rapid rehabilitation is widely accepted,and it is very difficult to set up a randomized controlled trial to compare robotic,VATS,and thoracotomy procedures for the treatment of NSCLC.Therefore,to overcome this limitation and to minimize bias,the best approach is to use a registry and prospectively collected,propensity score-matched data.Conclusions:Robotic lung resections result in similar long-term survival as compared with VATS and thoracotomy.Robot-assisted and VATS procedures are associated with short lengths of hospital stay,and the robotic procedure in particular results in superior lymph node assessment.Considering the alarming increase in the incidence of lung cancer in China,a nationwide database of prospectively collected data available for clinical research would be especially important.

CONVERSION OF UNSATURATED LONG－CHAIN FATTY ACIDS TO 10－HYDROXY FATTY ACIDS BY RESTING CELLS OF Nocardia sp

Resting cells of Nocardia sp.were used to convert a series of unsaturated long-chain fatty acids to 10-hvdroxy fatty acids.Structures of all metabolites were suggested by 1Hnuclear magnetic resonance and mass spectrum.The results showed that the hydroxylation sterospecificity happened at the cis-9 double bond with other position unaffected.

Long non-coding RNA SNHG16 promotes human placenta-derived mesenchymal stem cell proliferation capacity through the PI3K/AKT pathway under hypoxia

BACKGROUND The effect of hypoxia on mesenchymal stem cells(MSCs)is an emerging topic in MSC biology.Although long non-coding RNAs(lncRNAs)and messenger RNAs(mRNAs)are reported to play a critical role in regulating the biological characteristics of MSCs,their specific expression and co-expression profiles in human placenta-derived MSCs(hP-MSCs)under hypoxia and the underlying mechanisms of lncRNAs in hP-MSC biology are unknown.AIM To reveal the specific expression profiles of lncRNAs in hP-MSCs under hypoxia and initially explored the possible mechanism of lncRNAs on hP-MSC biology.METHODS Here,we used a multigas incubator(92.5%N_(2),5%CO_(2),and 2.5%O_(2))to mimic the potential of hP-MSCs.RNA sequencing technology was applied to identify the exact expression profiles of lncRNAs and mRNAs under hypoxia.RESULTS We identified 289 differentially expressed lncRNAs and 240 differentially expressed mRNAs between the hypoxia and normoxia groups.Among them,the lncRNA SNHG16 was upregulated under hypoxia,which was also validated by reverse transcription-polymerase chain reaction.SNHG16 was confirmed to affect hP-MSC proliferation rates using a SNHG16 knockdown model.SNHG16 overexpression could significantly enhance the proliferation capacity of hP-MSCs,activate the PI3K/AKT pathway,and upregulate the expression of cell cycle-related proteins.CONCLUSION Our results revealed the specific expression characteristics of lncRNAs and mRNAs in hypoxiacultured hP-MSCs and that lncRNA SNHG16 can promote hP-MSC proliferation through the PI3K/AKT pathway.

Long-term phenotypic characterization of human bone marrow and adipose tissue derived mesenchymal stromal cells

We present methods to characterize mesenchymal stromal cells (MSC) over long time periods in vitro. The methods entail passaging cells multiple times and performing differentiation studies with the cells at each passage. Using an array of surface markers and flow cytometric quantification, the data can be correlated to traditional measures of differentiation such as PCR and staining. Using these methods to quantify the amount of differentiation, we concluded that many common MSC markers do not specifically define MSCs with true stem cell properties. Additionally, adipose-derived as opposed to bone marrow-derived MSCs show long-term CD34+ labeling. The methods described can be used to help identify stem cell markers and to characterize the state of stem cells in vitro. Compiling these data from multiple laboratories would be helpful to determine source, extraction and culture methods needed to obtain high yields of useful stem cells.

Long noncoding RNAs in mesenchymal stromal/stem cells osteogenic differentiation:Implications in osteoarthritis pathogenesis

This letter focuses on a recently published article that provided an exceptional description of the effect of epigenetic modifications on gene expression patterns related to skeletal system remodeling.Specifically,it discusses a novel modality of epigenetic regulation,the long noncoding RNAs(lncRNAs),and provides evidence of their involvement in mesenchymal stromal/stem cells osteo-/adipogenic differentiation balance.Despite focus on lncRNAs,there is an emerging cross talk between lncRNAs and miRNAs interaction as a novel mechanism in the regulation of the function of the musculoskeletal system,by controlling bone homeostasis and bone regeneration,as well as the osteogenic differentiation of stem cells.Thus,we touched on some examples to demonstrate this interaction.In addition,we believe there is still much to discover from the effects of lncRNAs on progenitor and non-progenitor cell differentiation.We incorporated data from other published articles to review lncRNAs in normal progenitor cell osteogenic differentiation,determined lncRNAs involved in osteoarthritis pathogenesis in progenitor cells,and provided a review of lncRNAs in non-progenitor cells that are differentially regulated in osteoarthritis.In conclusion,we really enjoyed reading this article and with this information we hope to further our understanding of lncRNAs and mesenchymal stromal/stem cells regulation.

Sustained long-term clinical and radiological response with sunitinib for metastatic renal-cell carcinoma (RCC)

The authors herein report the case of a 67-year-old woman with metastatic renal-cell carcinoma (RCC), who has had a sustained clinical and stable radiological response to long-term therapy with an oral multi-targeted tyrosine kinase inhibitor (TKI), sunitinib with minimal lasting toxicity.

Analysis of long noncoding RNA-associated competing endogenous RNA network in glucagon-like peptide-1 receptor agonist-mediated protection inβcells

BACKGROUND Long noncoding RNAs(lncRNAs)and mRNAs are widely involved in various physiological and pathological processes.The use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)is a novel therapeutic strategy that could promote insulin secretion and decrease the rate ofβ-cell apoptosis in type 2 diabetes mellitus(T2DM)patients.However,the specific lncRNAs and mRNAs and their functions in these processes have not been fully identified and elucidated.AIM To identify the lncRNAs and mRNAs that are involved in the protective effect of GLP-1RA inβcells,and their roles.METHODS Rat gene microarray was used to screen differentially expressed(DE)lncRNAs and mRNAs inβcells treated with geniposide,a GLP-1RA.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to assess the underlying functions of DE mRNAs.Hub mRNAs were filtered using the STRING database and the Cytoscape plugin,CytoHubba.In order to reveal the regulatory relationship between lncRNAs and hub mRNAs,their co-expression network was constructed based on the Pearson coefficient of DE lncRNAs and mRNAs,and competing endogenous RNA(ceRNA)mechanism was explored through miRanda and TargetScan databases.RESULTS We identified 308 DE lncRNAs and 128 DE mRNAs with a fold change filter of≥1.5 and P value<0.05.GO and KEGG pathway enrichment analyses indicated that the most enriched terms were G-protein coupled receptor signaling pathway,inflammatory response,calcium signaling pathway,positive regulation of cell proliferation,and ERK1 and ERK2 cascade.Pomc,Htr2a,and Agtr1a were screened as hub mRNAs using the STRING database and the Cytoscape plugin,CytoHubba.This result was further verified using SwissTargetPrediction tool.Through the co-expression network and competing endogenous(ceRNA)mechanism,we identified seven lncRNAs(NONRATT027738,NONRATT027888,NONRATT030038,etc.)co-expressed with the three hub mRNAs(Pomc,Htr2a,and Agtr1a)based on the Pearson coefficient of the expression levels.These lncRNAs regulated hub mRNA functions by competing with six miRNAs(rno-miR-5132-3p,rno-miR-344g,rno-miR-3075,etc.)via the ceRNA mechanism.Further analysis indicated that lncRNA NONRATT027738 interacts with all the three hub mRNAs,suggesting that it is at a core position within the ceRNA network.CONCLUSION We have identified key lncRNAs and mRNAs,and highlighted here how they interact through the ceRNA mechanism to mediate the protective effect of GLP-1RA inβcells.