Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background: LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers. Nevertheless, the impacts of DLX6-AS1 on endometrial cancer (EC) development remained obscure. The study explored the influence of DLX6-AS1 on EC progression via the microRNA (miR)-374a-3p/zinc-finger protein (ZFX) axis.Methods: EC cell lines were collected and DLX6-AS1, miR-374a-3p, and ZFX levels in EC cell lines were detected. The EC cells were transfected with DLX6-AS1, miR-374a-3p, and ZFX constructs to examine the biological functions of EC cells. The xenograft model was established for detecting tumor growth. Rescue experiments were conducted to verify the interaction of DLX6-AS1, miR-374a-3p, and ZFX in EC cells.Results: DLX6-AS1 and ZFX levels were elevated, while miR-374a-3p exhibited a reduced level in EC cells. Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells. Reduced DLX6-AS1 repressed tumor development. MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing, while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth. Mechanically, DLX6-AS1 was found to bind to miR-374a-3p, and miR-374a-3p targeted ZFX.Conclusion: DLX6-AS1 depletion restricts the malignant phenotype of EC cells. The study might provide novel therapeutic biomarkers for EC treatment.     

Ginsenoside Rg1 protects against ischemia-induced neuron damage by regulating the rno-miRNA-27a-3p/PPARγ axis

Background: A preliminary miRNA screening showed that expression levels of rno-miRNA-27a-3p were significantly increased in the serum and brain tissues of rats undergoing cerebral ischemia. In recent years, there is evidence of the protective capacity of the saponins extracted from panax ginseng and its primary active ingredient ginsenosideRg1oncerebral ischemic injury. Methods: Fetal rat neurons (FRNs) were cultured in glucose-and-serum-free medium and exposed to hypoxia to establish a cerebral ischemia model in vitro (oxygen and glucose deprivation model, OGD). Antioxidant indexes (CAT, SOD), inflammatory markers (MPO, TNF-α and IL-6), and the expression of apoptosis and proliferation associated proteins (NF kB-p65, Caspase 3-cleaved, BCL-2) were examined. Results: Pre-treatment of Rg1 (30–100 μg/mL) could effectively inhibit the decline of antioxidant indexes (CAT, SOD) and increase in inflammatory markers (MPO, TNF-α and IL-6), and effectively inhibited the apoptosis in FRNs induced by OGD in a gradient-dependent manner. The mechanism analysis showed that the role of Rg1 in protecting against ischemia-induced neuron damage depends on its indirect up-regulation of PPAR protein via suppression of rno-miRNA-27a-3p. Moreover, these effects of Rg1 could be reversed by exogenous rno-miRNA-27a-3p and PPAR gene silencing in FRNs exposed to OGD. Conclusion: To summarize, our study demonstrates that Rg1 could effectively attenuate neuronal damage caused by cerebral ischemia via the rno-miRNA-27a-3p/PPARγ pathway. Further, clarification of the novel mechanism will certainly improve our previous understanding of the role of Rg1 and enhancing its level in treatments for alleviating ischemic brain injury.     

<i>LINC00609</i> inhibits A549 cells progression through the regulation of <i>miR-128-3p/RND3</i> axis

Background: Long-chain non-coding RNA (lncRNA) LINC00609 is a potential tumor suppressor, but the mechanism of action in non-small cell lung cancer (NSCLC) is yet to be understood.Objectives: The effects of LINC00609 on A549 cell proliferation, apoptosis, and cell cycle arrest were investigated. Methods: The LINC00609 levels in NSCLC and normal tissues were analyzed by bioinformatics. Expressions of LINC00609, miR-128-3p, and Rho family GTPase 3 (RND3) in NSCLC cells (A549) were determined by qRT-PCR. Bioinformatics analysis predicted target genes and dual-luciferase reporter assays to ensure that LINC00609 targeted miR-128-3p and miR-128-3p targeted RND3. The proliferation of cells was determined using EDU and CCK-8. Flow cytometry was used to evaluate cell apoptosis rate and cell cycle. The western blotting assay identified proteins related to proliferation and apoptosis. Results: In NSCLC tissues, LINC00609 was expressed in low levels, while its high expression was associated with a higher survival rate. LINC00609 affected cell proliferation, apoptosis, cell cycle arrest, and expression of related proteins. Dual-luciferase reporter assay showed that LINC00609 binds specifically to miR-128-3p, and miR-128-3p binds to RND3. MiR-128-3p overexpression could neutralize the effects of LINC00609. A siRNA targeting RND3 could reverse the effect of the miR-128-3p inhibitor. Silencing RND3 resulted in a decrease in apoptosis rate and the number of cells in the S-phase and an increase in the number of cells in the G1-phase. Furthermore, phosphorylation levels of the AKT protein and mTOR protein, and Bcl2 expression, increased; however, the expression of RND3, Bax, and caspase3 decreased. Conclusions: LINC00609 regulated miR-128-3p/RND3 axis to modulate A549 cell proliferation, apoptosis, and cell cycle arrest. In the case of NSCLC, LINC00609 could be a potential target for therapy.     

Puerarin inactivates NLRP3-mediated pyroptotic cell death to alleviate cerebral ischemia/reperfusion (I/R) injury through modulating the LncRNA DUXAP8/miR-223-3p axis

NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion (I/R) injury, and the aim of this study is to investigate the potential utilization of the Chinese medicine, Puerarin, in treating this disease. Through conducting in vitro and in vivo experiments, the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8 (DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death, resulting in the attenuation of I/R injury. Specifically, the cerebral I/R injury in rat models and hypoxia/reoxygenation (H/R) in primary hippocampus neuron (PHN) cells were inducted, which were subsequently exposed to Puerarin treatment. As expected, we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells. Next, through bioinformatics analysis, we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA, and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells. Interestingly, we evidenced that Puerarin restrained LncRNA DUXAP8 expressions, but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells, and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p. Collectively, we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.     

<i>miR-103-3p</i> regulates the differentiation of bone marrow mesenchymal stem cells in myelodysplastic syndrome

The pathogenesis of myelodysplastic syndrome (MDS) may be related to the abnormal expression of microRNAs(miRNAs), which could influence the differentiation capacity of mesenchymal stem cells (MSCs) towards adipogenic andosteogenic lineages. In this study, exosomes from bone marrow plasma were successfully extracted and identified.Assessment of miR-103-3p expression in exosomes isolated from BM in 34 MDS patients and 10 controls revealed its0.52-fold downregulation in patients with MDS compared with controls (NOR) and was downregulated 0.55-fold inMDS-MSCs compared with NOR-MSCs. Transfection of MDS-MSCs with the miR-103-3p mimic improved osteogenicdifferentiation and decreased adipogenic differentiation in vitro, while inhibition of miR-103-3p showed the oppositeresults in NOR-MSCs. Thus, the expression of miR-103-3p decreases in MDS BM plasma and MDS-MSCs, significantlyimpacting MDS-MSCs differentiation. The miR-103-3p mimics may boost MDS-MSCs osteogenic differentiation whileweakening lipid differentiation, thereby providing possible target for the treatment of MDS pathogenesis.     

Chrysophanol inhibits the progression of gastric cancer by activating nod-like receptor protein-3

Aim: Gastric cancer (GC) is one of the most common malignant tumors. Chrysophanol has been reported topossess antitumor effects on a variety of cancers; however, its role in GC remains unclear. This study aimed to investigatethe effects of chrysophanol on the proliferation, pyroptosis, migration, and invasion of GC cells. Methods: Human GCcell lines MKN 28 and AGS cells were treated with different concentrations of chrysophanol, then cell proliferation,migration, invasion and pyroptosis were determined by CCK-8, colony-forming assay, wound healing assay, Transwellassay, and flow cytometry. Cell migration and invasion were reassessed in these transfected cells following thetransfection of nod-like receptor protein-3 (NLRP3) siRNA in MKN 28 and AGS cells. To examine the downstreamsignaling pathway of the NLRP3 signaling pathway, NLRP3, caspase-1, gasdermin-D, interleukin (IL)-1β, and IL-18were detected by quantitative real-time-polymerase chain reaction or western blotting. Results: Chrysophanolinhibited the proliferation of GC cells, caused pyroptosis, inhibited cell migration and invasion, and increased theexpression of NLRP3 inflammasomes in GC cells. Knockdown of NLRP3 inhibited the effects of chrysophanol onproliferation, pyroptosis, migration, and invasion of GC cells. Chrysophanol plays an anticancer role by enhancingNLRP3. Conclusions: Chrysophanol exerts anti-neoplastic effects in vitro in GC cells by modulating NLRP3, thushighlighting its therapeutic potential in GC.     

Effect of microRNA-143-3p-mediated CTNND1 on the biological function of lung cancer cells

Lung cancer poses a serious threat to human life with high incidence and miRNA is an important biomarkerin tumors. This study aimed to explore the effect of miR-143-3p on the biological function of lung cancer cells and theunderlying mechanism. Eighty-seven samples of lung cancer tissues and 81 samples of tumor-adjacent tissues frompatients undergoing radical lung cancer surgery in our hospital were collected. The lung cancer cells and lung fibroblastcells (HFL-1) were purchased, and then miR-143-3p-mimics, miR-NC, si-CTNND1, and NC were transfected intoA549 and PC-9 cells to establish cell models. MiR-143-3p and CTNND1 expression levels were measured by the qRTPCR,Bax, Bcl-2, and CTNND1 expression levels by the Western Blot (WB), and cell proliferation, invasion, andapoptosis by the MTT assay, Transwell assay, and flow cytometry. Dual luciferase report assay was used to determinethe relationship between miR-143-3p and CTNND1. In this study, miR-143-3p was lowly expressed in lung cancerand CTNND1 was highly expressed in lung cancer. The overexpression of miR-143-3p inhibited cell proliferationand invasion, promoted cell apoptosis, significantly increased Bax protein expression, and decreased Bcl-2 proteinexpression. The inhibition of CTNND1 led to opposite biological characteristic in cells. The dual luciferase reporterassay demonstrated that miR-143-3p was a target region of CTNND1. Such results suggest that miR-143-3p can inhibitthe proliferation and invasion of lung cancer cells by regulating the expression of CTNND1 and promote the apoptosisof lung cancer cells, sott is expected to be a potential target for lung cancer.     

MiR-194-5p suppresses the warburg effect in ovarian cancer cells through the IGF1R/PI3K/AKT axis

Background: The Warburg effect is considered as a hallmark of various types of cancers, while the regulatorymechanism is poorly understood. Our previous study demonstrated that miR-194-5p directly targets and regulatesinsulin-like growth factor1 receptor (IGF1R). In this study, we aimed to investigate the role of miR-194-5p in theregulation of the Warburg effect in ovarian cancer cells. Methods: The stable ovarian cell lines with miR-194-5poverexpression or silencing IGF1R expression were established by lentivirus infection. ATP generation, glucose uptake,lactate production and extracellular acidification rate (ECAR) assay were used to analyze the effects of aerobic glycolysisin ovarian cancer cells. Gene expression was analyzed by quantitative polymerase chain reaction (qPCR) and westernblot. Immunohistochemistry assays were performed to assess the expression of the IGF1R protein in ovarian cancertissues. Results: Overexpression of miR-194-5p or silencing IGF1R expression in ovarian cancer cells decreases ATPgeneration, glucose uptake, lactate production, and ECAR and inhibits both the mRNA and protein expression ofPKM2, LDHA, GLUT1, and GLUT3. While the knockdown of miR-194-5p expression led to opposite results.Overexpression of miR-194-5p or silencing IGF1R expression suppressed the phosphatidylinositol-3-kinase/proteinkinase B (PI3K/AKT) pathway, whose activation can sustain aerobic glycolysis in cancer cells, and the knockdown ofmiR-194-5p expression promoted the activation of the PI3K/AKT pathway. Conclusion: Our results suggest that miR-194-5p can inhibit the Warburg effect by negative regulation of IGF1R and further repression of the PI3K/AKTpathway, which provides a theoretical basis for further test of miR-194-5p as a target in the treatment of ovarian cancer.     

Uncoupling tumor necrosis factor-α and interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

Triple Negative Breast Cancer (TNBC) immunotherapy has recently shown promising approach. However, some TNBC patients presented with resistance. One of the reasons was attributed to the excessive release of cytokines at the tumor microenvironment (TME) such as Tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Fine regulation of these cytokines’ levels via non-coding RNAs (ncRNAs) might alleviate the immune quiescent nature of TME at TNBC tumors. However, the extrapolation of ncRNAs as therapeutic tools is highly challenging. Therefore, disentanglement the nature for the isolation of natural compounds that could modulate the ncRNAs and their respective targets is an applicable translational therapeutic approach. Hence, this study aimed to targeting the chief immune suppressive cytokines at the TME (TNF-α and IL-10) via ncRNAs and to examine the effects of Rosemary aerial parts extract on the expression levels of these ncRNAs in TNBC. Results revealed miR-17-5p as a dual regulator of TNF-α and IL-10. Moreover, an intricate interaction has been shown between miR-17-5p and the oncogenic lncRNAs: MALAT1 and H19. Knocking down of MALAT1 and/or H19 caused an induction in miR-17-5p and reduction in TNF-α and IL-10 expression levels. miR-17-5p was found to be down-regulated, while TNF-α, IL-10, MALAT1 and H19 were up-regulated in BC patients. Forced expression of miR-17-5p in MDA-MB-231 cells reduced TNF-α, IL-10, MALAT1 and H19 expression levels, as well as several BC hallmarks. In a translational approach, ursolic acid (UA) isolated from rosemary induced the expression of miR-17-5p, MALAT1 and decreased H19 expression levels. In conclusion, this study suggests miR-17-5p as a tumor suppressor and an immune-activator miRNA in BC through tuning up the immunological targets TNF-α, IL-10 at the TME and the oncological mediators MALAT1 and H19 lncRNAs.     

Epithelial-mesenchymal transition contributes to malignant phenotypes of circulating tumor cells derived from gastric cancer

Circulating tumor cells (CTCs) are crucial to tumor metastasis, and they usually undergo epithelial–mesenchymal transition (EMT) in order to disseminate from the primary tumor. However, very little is currentlyknown about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer.Therefore, this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived fromgastric cancer cells. We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1(TGFβ-1) into nude mice by intravenous injection. Next, we isolated CTCs from the blood of nude mice by gradientcentrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increasedviability and invasion ability compared to MKN28 cells without TGFβ-1 treatment. Immunocytochemical stainingshowed lower expression of E-cadherin and higher expression of N-cadherin, vimentin, and β-catenin in CTCs derivedfrom MKN28 cells pretreated with TGFβ-1. Furthermore, the expression of Wnt3a, β-catenin, cyclin D1, and c-Mycwas significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1. Taken together, these findingssuggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells. Furthermore, the malignantphenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells. Targeting EMT inCTCs is a new approach to the treatment of gastric cancer relapse and metastasis.     

High level of circPTN promotes proliferation and stemness in gastric cancer

Increasing evidence proves that circular RNAs (circRNAs) play an important role in regulating the biological behaviors of tumors. The central purpose of this research was to investigate the functions of circRNA in gastric cancer. The utilization of real-time PCR was to test circPTN expression in gastric cancer cells. Cell counting colony formation assays, CCK-8 assay, and EdU assay were used to investigate proliferation. Transwell assay was applied to investigate migration. We discovered that circPTN was highly expressed in gastric cancer cells. Low expression of circPTN inhibits gastric cancer cell proliferation and migration. Elevated expression of circPTN promotes gastric cancer cell proliferation and migration. Moreover, we discovered that circPTN could accelerate self-renewal and increase the expression of stemness markers. The results of our study suggested that a high level of circPTN expression promotes the proliferation and stemness of gastric cancer cells.     

SR-BI expression regulates the gastric cancer tumor immune microenvironment and is associated with poor prognosis

Aim: Scavenger receptor class B, type I (SR-BI) is an integral plasma membrane protein that has been reported to be overexpressed in various malignancies, such as renal cancer, breast cancer, and prostate cancer, and is an independent prognostic factor. However, the clinical value and expression of SR-BI in GC are unknown. Our research aimed to explore the role of SR-BI in combination with immune markers as a diagnostic and prognostic marker for gastric cancer (GC). Methods: GC tissues, paracancerous tissues, and clinicopathological data of 149 patients were collected. The expression level of SR-BI, Tumor-infiltrating lymphocytes (TILs), and PD-L1 were evaluated by immunohistochemistry (IHC). The associations of the SR-BI staining intensity with clinicopathological features and immune markers were determined by the chi-square test. Univariate and multivariate COX regression analyses were used to evaluate independent prognostic factors. Kaplan–Meier analyses were performed to plot the survival curve. Results: Our results indicated that SR-BI was expressed at higher levels in tumor tissues than in adjacent paracancerous tissues (p < 0.001), and patients with high levels of SR-BI expression had a worse prognosis. Univariate and multivariate analyses revealed that high SR-BI expression was an independent factor for poor prognosis. The chi-square test determined that the expression of SR-BI was negatively correlated with CD4+ T cells and CD8+ T cells (CD4+ T cells, p = 0.013; CD8+ T cells, p = 0.021), and positively correlated with PD-L1 (p = 0.022). Finally, survival analysis revealed that CD4+ T cells were associated with the prognosis of GC patients (p = 0.019), and the combined survival analysis of SR-BI and CD4+ T cells was also statistically significant (p = 0.030). Conclusion: SR-BI is highly expressed in GC tissue and associated with poor prognosis. Moreover, SR-BI can also regulate the GC tumor immune microenvironment.     

miRNA-148b-3p targeting SOCS3 inhibits macrophage M2 polarization by JAK2/STAT3 pathway in immune thrombocytopenia

Aberrant expression of miRNAs is significantly correlated with the occurrence of immune thrombocytopenic purpura (ITP). The immune imbalance of M1/M2 macrophage contributes to the development of ITP. However, the role of miR-148b-3p in macrophage phenotype imbalance remains unknown in ITP. In this study, we aimed to explore whether miR-148b-3p inhibits M2 macrophage polarization in ITP and to investigate the underlying mechanism. Peripheral blood from 22 ITP patients were collected, and real-time PCR confirmed that miR-148b-3p was up-regulated and Western blot analyses detected the expression of SOCS3 was down-regulated. Subsequent dual-luciferase reporter gene assay indicated that miR-148b-3p could bind to SOCS3. Furthermore, we found significant correlation between miR-148b-3p expression and platelet count. Applying gain and lose the function experiments of miR-148b-3p and SOCS3, we demonstrated that suppression of miR-148b-3p or up-regulation of SOCS3 promoted macrophage M2 polarization by inhibiting JAK2/STAT3 pathway. Together, our findings demonstrate that that miR-148b-3p targeting SOCS3 inhibits M2 macrophage polarization via JAK2/STAT3 signaling in ITP.     

Knockdown of lncRNA XIST prevents the epithelial-mesenchymal transition of TGF-β2-induced human lens epithelial cells via miR-124/Slug axis

Posterior capsular opacification (PCO) is linked to the pathological process of lens epithelial cells, which includes proliferation, migration, and epithelial-mesenchymal transition (EMT). Our goal was to investigate whether long noncoding RNA (lncRNA) XIST contributes to EMT via targeting miR-124/Slug axis in TGF-β2-induced SRA01/04 cells. EMT was induced by stimulating SRA01/04 cells with 10 ng/mL TGF-β2 for 24 h, and PCO microenvironment was simulated. The expressions levels of lncRNA XIST, miR-124, and Slug were measured by real-time polymerase chain reaction (RT-PCR) and western blot. The role and mechanism of lncRNA XIST in promoting EMT of TGF-β2-treated SRA01/04 cells were investigated by using cell transfection, cell counting kit-8 (CCK-8), immunofluorescence staining, transwell assay, wound-healing assay, RT-PCR, western blot and dual-luciferase reporter assay. The expression of Slug and lncRNA XIST was markedly increased, while miR-124 was downregulated in TGF-β2-treated SRA01/04 cells compared with the control group. Knockdown of lncRNA XIST reduced EMT, migration, and cell viability in TGF-β2-induced SRA01/04 cells; moreover, it adversely modulated miR-124 and adjusted the expression of Slug in SRA01/04 cells, while these effects were diminished by co-transfection with AMO-miR-124. Our data demonstrated that lncRNA XIST functioned as a competitive endogenous RNA (ceRNA) of miR-124 to modulate the expression level of Slug, thereby modulating EMT, migration, and cell viability in SRA01/04 cells. In conclusion, lncRNA XIST has a crucial role in promoting TGF-β2-induced EMT via modulating the miR-124/Slug axis in SRA01/04 cells, and it may provide a novel therapeutic option for PCO treatment.     

Construction and validation of prognostic model based on autophagy-related lncRNAs in gastric cancer

Gastric cancer (GC) is one of the most common cancer worldwide. Although emerging evidence indicates thatautophagy-related long non-coding RNA (lncRNA) plays an important role in the progression of GC, the prognosis ofGC based on autophagy is still deficient. The Cancer Genome of Atlas stomach adenocarcinoma (TCGA-STAD) datasetwas downloaded and separated into a training set and a testing set randomly. Then, 24 autophagy-related lncRNAs werefound strongly associated with the survival of the TCGA-STAD dataset. 11 lncRNAs were selected to build the risk scoremodel through the least absolute shrinkage and selection operator (LASSO) regression. Every patient got a risk score (RS),and patients were separated into a high-risk group and a low-risk group due to the median RS. The multivariate Coxanalysis showed that the RS could be an independent prognosis predictor. The Kaplan-Meier survival analysis and theReceiver Operating Characteristic (ROC) curve indicated the model had an excellent prediction effect. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the mRNAs in the prognosticnetwork were mainly involved in the autophagy and ubiquitin-like protein ligase binding. Gene Set EnrichmentAnalysis (GSEA) analysis uncovered that the differentially expressed genes (DEGs) in the high-risk group partiallyparticipated in the ECM receptor interaction and other signaling pathways. Our results indicated that the risk scoremodel based on the autophagy-related lncRNAs performed well in the prediction of prognosis for patients with GC.     

Dihydropyrimidinase like 3 as a novel target of wild type p53 suppresses MAPK pathway in response to hypoxia

Endometrial cancer remains to be a major type of malignancy in threatening female life. Molecular insights in advancing our understanding of endometrial tumorigenesis are much needed. We here report that a less-studied protein Dihydropyrimidinase like 3 (DPYSL3) is a potent tumor suppressor. DPYSL3 is uniquely regulated by wild type p53 (wtp53), and its expression is at the highest level when cells carry wtp53 and are exposed to hypoxia. We reveal that wtp53 can bind DPYSL3 promoter to enhance DPYSL3 expression and in turn, the elevated DPYSL3 can restrain cancer cell proliferation and invasion in vitro and in vivo. Importantly, we observe that DPYSL3 can interfere with MAP kinase pathway, supported by a substantially reduced level of phosphorylated ERK in cells with high expression of DPYSL3. Furthermore, we identify the specific region of DPYSL3 that is responsible for its interaction with MEK and a subsequently reduced activity of ERK. In combination of molecular docking and mutagenesis analysis, we validated that the therapeutic implication of 17 A.A.s of DPYSL3, which can reduce the activity of the MAPK pathway and inhibit endometrial tumor cell growth in vitro and in vivo. Therefore, our study not only demonstrates in-depth understanding of human tumorigenesis, especially endometrial tumor, but also only provides a therapeutic potential to develop an effective tool to fight against human malignancy.