Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SLFN5 influences proliferation and apoptosis by upregulating PTEN transcription via ZEB1 and inhibits the purine metabolic pathway in breast cancer

ABSTRACT: Human Schlafen-5 (SLFN5) is aberrantly involved in tumorigenesis in several types of cancer. However, its implications in breast cancer (BRCA) are unknown. Herein, we demonstrated that SLFN5 expression is negatively associated with the tumour growth of human BRCA using GEO database analysis and clinical sample immunostaining. Lentiviral overexpression of SLFN5 in BRCA cell lines suppressed tumourigenicity in nude mice. Knockdown and overexpression of SLFN5 in BRCA cell lines proved that SLFN5 can inhibit cell proliferation and colony formation and promote apoptosis by upregulating the transcription of a known cancer suppressor gene (the phosphatase and tensin homologue on chromosome 10, PTEN), resulting in molecular changes in the downstream AKT pathway and in proliferation/apoptosis. Lentiviral knockdown and overexpression of ZEB1 blocked the changes in the PTEN and AKT pathways and in the colony formation ability caused by SLFN5 knockdown and overexpression, respectively. Luciferase reporter assays demonstrated that ZEB1 can inhibit the PTEN promoter activity in MCF7 cells by binding to a motif in the PTEN promoter. Metabonomics analysis showed that SLFN5 influences many metabolic pathways and especially decreases purine metabolites, including inosine, xanthine, and hypoxanthine. In conclusion, our findings suggest that SLFN5 may be an important protective factor against BRCA, as it regulates PTEN transcription, the AKT pathway, and proliferation/apoptosis via ZEB1 mediation and inhibits the purine metabolic pathway. Thus, SLFN5 may be a potential therapeutic target for BRCA.

SUBMITTER: Gu X

PROVIDER: S-EPMC7539779 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Downregulation of long non-coding RNA NR2F2-AS1 inhibits proliferation and induces apoptosis of nasopharyngeal carcinoma cells by upregulating the expression of PTEN.

Project description:The novel long non-coding RNA NR2F2-AS1 has been characterized as an oncogene in lung cancer. The present study aimed to investigate the role of NR2F2-AS1 in nasopharyngeal carcinoma (NPC). The results demonstrated that expression of NR2F2-AS1 and phosphatase and tensin homolog (PTEN) were negatively associated with each other in NPC tissues. Furthermore, upregulated NR2F2-AS1 expression levels and downregulated PTEN expression levels in NPC tissues predicted less favorable survival outcomes in patients with NPC. Transfection of NPC cells with NR2F2-AS1 small interfering RNA resulted in increased expression of PTEN. In addition, NR2F2-AS1 silencing and PTEN overexpression resulted in decreased proliferation and an increase in the apoptotic rate of NPC cells. In conclusion, NR2F2-AS1 downregulation decreased proliferation and increased apoptosis of NPC cells via upregulation of PTEN.

| S-EPMC6955651 | biostudies-literature

TRIM14 promotes cell proliferation and inhibits apoptosis by suppressing PTEN in colorectal cancer.

Project description:Background:Colorectal cancer (CRC) is among the most frequent and lethal malignancies worldwide. Although great advances have been made in the treatment of CRC, prognosis remains poor. Our previous study indicated that tripartite motif-containing 14 (TRIM14) was upregulated in CRC samples. Methods:In the current study, the association between TRIM14 and CRC was investigated. Protein expression was determined by Western blotting and immunohistochemistry. Further, the biological roles of TRIM14 in CRC cell proliferation and apoptosis were explored both in vitro and in vivo. Results:We observed that increased TRIM14 expression in CRC tissues was closely related with aggressive clinicopathological characteristics and poor prognosis. TRIM14 knockdown markedly reduced proliferation and increased apoptosis in HT-29 and SW620 cells, whereas TRIM14 overexpression in LoVo cells displayed opposite results. Xenograft experiments using HT-29 cells confirmed suppression of tumor growth and induction of apoptosis upon TRIM14 knockdown in vivo. Furthermore, downregulation of TRIM14 inhibited the AKT pathway, as indicated by reduced levels of phosphorylated AKT, Bcl-2 and Cyclin D1, and elevated levels of phosphatase and tensin homology (PTEN) and p27. In addition, TRIM14 colocalized with PTEN in the cytoplasm and induced PTEN ubiquitination. Moreover, PTEN overexpression significantly inhibited pro-proliferative effects of TRIM14, indicating an involvement of PTEN/AKT signaling in mediating TRIM14 functions. Conclusions:The present data demonstrate that TRIM14 overexpression promotes CRC cell proliferation, suggesting TRIM14 as an attractive therapeutic target for CRC.

| S-EPMC6598940 | biostudies-literature

LncRNA MORT Inhibits Cancer Cell Proliferation and Promotes Apoptosis in Mantle Cell Lymphoma by Upregulating miRNA-16.

Project description:Introduction:LncRNA mortal obligate RNA transcript (MORT) is downregulated in different types of cancer, indicating its involvement in cancer biology. Methods:In this study, MORT and miRNA-16 were both downregulated in plasma of mantle cell lymphoma (MCL) patients than that in the controls. The low levels of MORT and miRNA-16 were correlated with poor survival of MCL patients. The expression of MORT and miRNA-16 was positively correlated only in MCL patients. Results:Overexpression of MORT and miRNA-16 suppressed cell proliferation but promoted cancer cell apoptosis, while miRNA-16 inhibitor reduced the effects of MORT overexpression. Overexpression of MORT led to upregulated expression of miRNA-16, while overexpression of miRNA-16 had no effect on the expression of MORT. Conclusion:Therefore, MORT may inhibit cancer cell proliferation and promote apoptosis in mantle cell lymphoma by upregulating miRNA-16.

| S-EPMC7127878 | biostudies-literature

mi-R4435-2HG promotes proliferation and inhibits apoptosis of cancer cells in ovarian carcinoma by upregulating ROCK2.

Project description:The present study aimed to investigate the involvement of long noncoding RNA mi-R4435-2HG in ovarian carcinoma. mi-R4435-2HG and Rho-associated protein kinase 2 (ROCK2) were demonstrated to both be upregulated in ovarian carcinoma. mi-R4435-2HG and ROCK2 were positively correlated in both tumor and healthy tissues. mi-R4435-2HG overexpression mediated the upregulation of ROCK2, while upregulation of ROCK2 did not affect mi-R4435-2HG. Overexpression of mi-R4435-2HG and ROCK2 led to promoted proliferation and inhibited apoptosis of cancer cells, while mi-R4435-2HG and ROCK2 knockdown had the opposite effect. In addition, ROCK2 knockdown attenuated the effects of mi-R4435-2HG overexpression on cancer cell proliferation and apoptosis. Therefore, mi-R4435-2HG promotes proliferation and inhibits apoptosis of cancer cells in ovarian carcinoma by upregulating ROCK2.

| S-EPMC6956214 | biostudies-literature

ROCK2 Confers Acquired Gemcitabine Resistance in Pancreatic Cancer Cells by Upregulating Transcription Factor ZEB1.

Project description:Resistance to chemotherapy is a major clinical challenge in the treatment of pancreatic ductal adenocarcinoma (PDAC). Here, we provide evidence that Rho associated coiled-coil containing protein kinase 2 (ROCK2) maintains gemcitabine resistance in gemcitabine resistant pancreatic cancer cells (GR cells). Pharmacological inhibition or gene silencing of ROCK2 markedly sensitized GR cells to gemcitabine by suppressing the expression of zinc-finger-enhancer binding protein 1 (ZEB1). Mechanically, ROCK2-induced sp1 phosphorylation at Thr-453 enhanced the ability of sp1 binding to ZEB1 promoter regions in a p38-dependent manner. Moreover, transcriptional activation of ZEB1 facilitated GR cells to repair gemcitabine-mediated DNA damage via ATM/p-CHK1 signaling pathway. Our findings demonstrate the essential role of ROCK2 in EMT-induced gemcitabine resistance in pancreatic cancer cells and provide strong evidence for the clinical application of fasudil, a ROCK2 inhibitor, in gemcitabine-refractory PDAC.

| S-EPMC6966455 | biostudies-literature

Human Schlafen 5 Inhibits Proliferation and Promotes Apoptosis in Lung Adenocarcinoma via the PTEN/PI3K/AKT/mTOR Pathway.

Project description:BackgroundHuman Schlafen 5 (SLFN5) is reported to inhibit or promote the proliferation of several specific types of cancer cells by our lab and other researchers. We are curious about its implications in lung adenocarcinoma (LUAC), a malignant tumor with a high incidence rate and high mortality.MethodLentiviral stable transfections of SLFN5-specific shRNA for knockdown and SLFN5 full-length coding sequence for overexpression were performed in LUAC cell for proliferation analysis in vitro and in vivo in nude mice. Clinical LUAC samples were collected for immunohistochemical analysis of SLFN5 protein levels.ResultsWe found that knockdown of endogenous SLFN5 upregulates cancer cell proliferation while inhibiting apoptosis. Besides, SLFN5 inhibition on proliferation was also observed in a nude mouse xenograft model. In contrast, overexpression of exogenous SLFN5 inhibited cell proliferation in vitro and in vivo and promoted apoptosis. As to the signaling pathway, we found phosphatase and tensin homolog on chromosome 10 (PTEN) was positively regulated by SLFN5, while its downstream signaling pathway AKT/mammalian target of rapamycin (mTOR) was inhibited. Moreover, compared with adjacent normal tissues, SLFN5 protein levels were markedly decreased in lung adenocarcinoma tissues. In conclusion, these suggest that human SLFN5 plays inhibitory roles in LUAC progression through the PTEN/PI3K/AKT/mTOR pathway, providing a potential target for developing drugs for lung cancer therapy in the future.

| S-EPMC8009730 | biostudies-literature

MiR-508-3p promotes proliferation and inhibits apoptosis of middle ear cholesteatoma cells by targeting PTEN/PI3K/AKT pathway.

Project description:Cholesteatoma of the middle ear is a common disease in otolaryngology, which can lead to serious intracranial and extracranial complications. Recent studies showed that the dysregulation of microRNA may be involved in the formation of middle ear cholesteatoma. This study aimed to explore the regulatory effect of micro ribonucleic acid 508-3p (miR-508-3p) on proliferation and apoptosis of middle ear cholesteatoma cells and excavate its underlying regulatory mechanism. We found miR-508-3p expression was upregulated in tissues and cells of cholesteatoma which was inversely related to the expression of hsa_circ_0000007. Overexpression of miR-508-3p could notably facilitate cholesteatoma cell proliferation. Luciferase reporter assay showed that miR-508-3p bound the 3'-untranslated region of its downstream mRNA PTEN. Gain and loss of functions of miR-508-3p were performed to identify their roles in the biological behaviors of cholesteatoma cells, including proliferation and apoptosis. Rescue assays confirmed that PTEN could reverse the effect of miR-508-3p overexpression on cell proliferation. In a word, this study validated that the development of cholesteatoma may regulated by hsa_circ_0000007/miR-508-3p/ PTEN/ PI3K/Akt axis.

| S-EPMC8364443 | biostudies-literature

Downregulation of EVI1 Expression Inhibits Cell Proliferation and Induces Apoptosis in Hilar Cholangiocarcinoma via the PTEN/AKT Signalling Pathway.

Project description:Aims: Hilar cholangiocarcinoma (HCCA) is a tumour with high malignancy, low surgical resection potential, and a poor prognosis. Ecotropic Viral Integration site 1 (EVI1) is a transcriptional regulator that has been proven to be associated with tumourigenesis and progression in many human solid tumours. However, the expression of EVI1 and its role in HCCA progression remain unclear. The aim of this study was to clarify the association between EVI1 expression and clinical outcomes in patients with HCCA. Methods: The expression of EVI1 in HCCA tissue samples and cell lines was examined by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC). Kaplan-Meier analysis was used for survival analysis. A log-rank test was performed for univariate analysis of survival, and a Cox regression model was utilized for multivariate analysis of survival. Cell proliferation was measured by cell counting kit-8 (CCK-8), colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. The cell cycle was evaluated by flow cytometry. Cell apoptosis was detected by flow cytometry and a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) assay. In vivo tumour growth was observed for xenografts in nude mice. Results: EVI1 expression was upregulated in HCCA tissue samples and correlated with a poor prognosis. In clinical specimens, the expression of EVI1 correlated with tumour histological grade and tumour size. Knocking down EVI1 expression reduced HCCA cell proliferation, blocked cell cycle progression, and promoted apoptosis in vitro and in vivo. Furthermore, we found that EVI1 could regulate the AKT signalling pathway by regulating PTEN levels in HCCA. Conclusion: Our data revealed that EVI1 played important roles in HCCA tumourigenesis and development. Our findings suggest that EVI1 may be a potentially useful therapeutic target in HCCA.

| S-EPMC6995371 | biostudies-literature

Histone demethylase Jumonji domain-containing 1A inhibits proliferation and progression of gastric cancer by upregulating runt-related transcription factor 3.

Project description:The histone demethylase Jumonji domain-containing 1A (JMJD1A) is overexpressed in multiple cancers and promotes cancer progression. However, the role and mechanism of JMJD1A in gastric cancer (GC) remains poorly understood. Here, we found that JMJD1A could suppress GC cell proliferation and xenograft tumor growth. Using RNA sequencing, we identified runt-related transcription factor 3 (RUNX3) as a novel target gene of JMJD1A. Mechanistically, we identified that JMJD1A upregulated RUNX3 through co-activating Ets-1 and reducing the H3K9me1/2 levels at the RUNX3 promoter in GC cells. Functionally, JMJD1A inhibits the growth of GC cells in vivo, which is partially dependent on RUNX3. Moreover, JMJD1A expression was decreased in GC and low expression of JMJD1A was correlated with an aggressive phenotype and a poor prognosis in patients with GC. Importantly, JMJD1A expression was positively associated with RUNX3 expression in GC samples. These studies indicated that JMJD1A upregulates RUNX3 expression via co-activation of transcription factor Ets-1 to inhibit proliferation of GC cells. Our findings provide new insight into the mechanism by which JMJD1A regulates RUNX3 transcription and suggest that JMJD1A and/or RUNX3 may be used as a therapeutic intervention for GC.

| S-EPMC7541000 | biostudies-literature

Downregulation of GRHL2 inhibits the proliferation of colorectal cancer cells by targeting ZEB1.

Project description:Previous reports have associated GRHL2 with tumor progression. However, the biological role of GRHL2 in human colorectal cancer (CRC) has not been explored. We examined the expression of GRHL2 in 75 CRC samples, as well as the paired non-tumor tissues, by immunohistochemistry, qRT-PCR, and western blot analysis. The association between GRHL2 expression and various clinicopathological parameters including Ki-67, a marker of proliferative activity, was also evaluated. We performed lentivirus-mediated shRNA transfection to knock down GRHL2 gene expression in HT29 and HCT116 CRC cells. Cell proliferation was examined by the CCK-8 (Cell Counting Kit-8) assay, colony formation, and cell cycle assay in vitro. Tumorigenesis in vivo was assessed using a mouse xenograft model. Moreover, we transiently silenced ZEB1 expression in GRHL2-knockdown CRC cells using specific shRNA, and then examined the effects on GRHL2 and E-cadherin expression, as well as cell proliferation. Herein, we demonstrated that enhanced GRHL2 expression was detected in CRC, and correlated with higher levels of Ki-67 staining, larger tumor size, and advanced clinical stage. Knocking down GRHL2 in HT29 and HCT116 CRC cells significantly inhibited cell proliferation by decreasing the number of cells in S phase and increasing that in the G 0/G 1 phaseof the cell cycle. This resulted in inhibition of tumorigenesis in vivo, as well as increased expression of ZEB1. Furthermore, transient ZEB1 knockdown dramatically enhanced cell proliferation and increased GRHL2 and E-cadherin expression. Collectively, our study has identified ZEB1 as a target of GRHL2 and suggested a reciprocal GRHL2-ZEB1 repressive relationship, providing a novel mechanism through which proliferation may be modulated in CRC cells.

| S-EPMC4100988 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data