17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway

AbstractOsteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The importance of chondrocytes in the pathogenesis of OA is unequivocal. 17β-estradiol (E2) has a potential protective effect against OA. However, the mechanism of E2 in OA chondrocytes remains unclear. In this study, we investigated the regulative effect of E2 on cell growth and the relationship between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with interleukin-1β). We found that E2 induced chondrocyte proliferation, and increased the expression level of Akt simultaneously, especially the expression level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte proliferation induced by E2. These results suggest that PI3K/Akt activation induced by E2 may be an important factor in the mechanism of E2 in cell proliferation in rat OA model chondrocytes, and help further understanding the role of E2 in OA progression.

Download Full-text

JAK2/STAT3 in role of arsenic-induced cell proliferation: a systematic review and meta-analysis

Reviews on Environmental Health ◽

10.1515/reveh-2021-0051 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Shugang Li ◽

Shanshan Ran ◽

Qingxin Ren

Keyword(s):

Cell Proliferation ◽

Meta Analysis ◽

Arsenic Concentration ◽

Arsenic Exposure ◽

Malignant Cell ◽

Dose Effect ◽

Expression Level ◽

Exposure Concentration ◽

Effect Relationship

Abstract Objectives Malignant cell proliferation is one of the important mechanisms of arsenic poisoning. A large number of studies have shown that STAT3 plays an important role in cell malignant proliferation, but there are still many contradictions in the effect of arsenic on JAK2/STAT3. This study aims to explore the role of JAK2/STAT3 in arsenic-induced cell proliferation. Methods By taking normal cells as the research object and using Standard Mean Difference (SMD) as the effect size, meta-analysis was used to explore the effect of arsenic on JAK2/STAT3. Then, the dose-effect Meta was used to further clarify the dose-effect relationship of arsenic on JAK2/STAT3. Results Through meta-analysis, this study found that arsenic could promote the phosphorylation of STAT3 (SMD=4.21, 95%CI [1.05, 7.37]), and increase IL-6 and p-JAK2, Vimentin, VEGF expression levels, thereby inducing malignant cell proliferation. In addition, this study also found that arsenic exposure dose (<5 μmol m−3), time(<24 h) and cell type were important sources of heterogeneity in the process of exploring the effects of arsenic on p-STAT3, IL-6 and p-JAK2. Dose-effect relationship meta-analysis results showed that arsenic exposure significantly increased the expression level of IL-6. When the arsenic exposure concentration was less than 7 μmol m−3, the expression level of p-JAK2 upregulated significantly as the arsenic exposure concentration gradually increasing. Moreover, the expression level of p-STAT3 elevated significantly with the gradual increase of the arsenic concentration under 5 μmol m−3 of arsenic exposure, but the expression level of p-STAT3 gradually decreases when the concentration is greater than 5 μmol m−3. Conclusions Exposure to low dose of arsenic could promote the expression of JAK2/STAT3 and induce the malignant proliferation of cells through upregulating IL-6, and there was dose-effect relationship among them.

Download Full-text

MiR199a is implicated in embryo implantation by regulating Grb10 in rat

Reproduction ◽

10.1530/rep-13-0290 ◽

2014 ◽

Vol 147 (1) ◽

pp. 91-99 ◽

Cited By ~ 12

Author(s):

Hong-Fei Xia ◽

Jing-Li Cao ◽

Xiao-Hua Jin ◽

Xu Ma

Keyword(s):

Cell Proliferation ◽

Embryo Implantation ◽

Growth Factor Receptor ◽

Inverse Association ◽

Loss Of Function ◽

Endometrial Stromal Cells ◽

Proliferation And Apoptosis ◽

17Β Estradiol

MiR199a was found to be differentially expressed in rat uteri between the prereceptive and receptive phase via microRNA (miRNA) microarray analysis in our previous study. However, the role of miR199a in rat embryo implantation remained unknown. In the study, northern blot results showed that the expression levels of miR199a were higher on gestation days 5 and 6 (g.d.5–6) in rat uteri than on g.d.3–4 and g.d.7–8. In situ localization of miR199a in rat uteri showed that miR199a was mainly localized in the stroma or decidua. The expression of miR199a was not significantly different in the uteri of pseudopregnant rats and evidently increased in the uteri of rats subjected to activation of delayed implantation and experimentally induced decidualization. Treatment with 17β-estradiol or both 17β-estradiol and progesterone significantly diminished miR199a levels. Gain of function of miR199a in endometrial stromal cells isolated from rat uteri inhibited cell proliferation and promoted cell apoptosis. Loss of function of miR199a displayed opposite roles on cell proliferation and apoptosis. Further investigation uncovered a significant inverse association between the expression of miR199a and growth factor receptor-bound protein 10 (Grb10), an imprinted gene, and miR199a could bind to the 3′UTR of Grb10 to inhibit Grb10 translation. In addition, in vivo analysis found that the immunostaining of GRB10 was attenuated in the stroma or decidua from g.d.4 to 6, contrary to the enhancement of miR199a. Collectively, upregulation of miR199a in rat uterus during the receptive phase is regulated by blastocyst activation and uterine decidualization. Enforced miR199a expression suppresses cell proliferation partially through targeting Grb10.

Download Full-text

17β-Estradiol abrogates apoptosis in murine skeletal muscle cells through estrogen receptors: role of the phosphatidylinositol 3-kinase/Akt pathway

Journal of Endocrinology ◽

10.1677/joe-07-0250 ◽

2007 ◽

Vol 196 (2) ◽

pp. 385-397 ◽

Cited By ~ 70

Author(s):

Andrea Vasconsuelo ◽

Lorena Milanesi ◽

Ricardo Boland

Keyword(s):

Skeletal Muscle ◽

Protective Action ◽

Muscle Cells ◽

Cellular Systems ◽

C2c12 Cells ◽

Skeletal Muscle Cells ◽

Akt Pathway ◽

Akt Activation ◽

17Β Estradiol ◽

Murine Skeletal Muscle

Estrogens can regulate apoptosis in various cellular systems. The present study shows that 17β-estradiol (E2), at physiological concentrations, abrogates DNA damage, poly (ADP-ribose) polymerase cleavage, and mitochondrial cytochrome c release induced by H2O2 or etoposide in mouse skeletal muscle C2C12 cells. This protective action, which involved PI3K/Akt activation and Bcl-2 associated death agonist (BAD) phosphorylation, was inhibited by antibodies against the estrogen receptor (ER) α or β isoforms, or transfecting siRNA specific for each isoform. The inhibition of the antiapoptotic action of E2 at the mitochondrial level was more pronounced when ER-β was immunoneutralized or suppressed by mRNA silencing, whereas transfection of C2C12 cells with either ER-α siRNA or ER-β siRNA blocked the activation of Akt by E2, suggesting differential involvement of ER isoforms depending on the step of the apoptotic/survival pathway evaluated. These results indicate that E2 exerts antiapoptotic effects in skeletal muscle cells which are mediated by ER-β and ER-α and involve the PI3K/Akt pathway.

Download Full-text

Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

Molecular Biology of the Cell ◽

10.1091/mbc.e04-07-0547 ◽

2005 ◽

Vol 16 (1) ◽

pp. 231-237 ◽

Cited By ~ 292

Author(s):

Filippo Acconcia ◽

Paolo Ascenzi ◽

Alessio Bocedi ◽

Enzo Spisni ◽

Vittorio Tomasi ◽

...

Keyword(s):

Cell Proliferation ◽

Estrogen Receptor ◽

Plasma Membrane ◽

Estrogen Receptor Α ◽

Membrane Localization ◽

Target Cells ◽

Dependent Manner ◽

Caveolin 1 ◽

17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

Download Full-text

USP46 inhibits cell proliferation in lung cancer through PHLPP1/AKT pathway

10.21203/rs.3.rs-18973/v1 ◽

2020 ◽

Author(s):

Wei Wang ◽

Meng Chen ◽

Hailing Xu ◽

Dongqing Lv ◽

Suna Zhou ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cancer Cell ◽

Lung Cancer Cells ◽

Akt Pathway ◽

Cancer Cell Proliferation ◽

Lung Cancer Cell ◽

Knock Down

Abstract Background: USP46 has been shown to function as tumor suppressor in colon cancer and renal cell carcinoma. However, its specific role in other cancers remains unknown. This study was aimed to investigate the role of USP46 in lung cancer tumorigenesis, and to identify the underlying mechanism. Methods: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western Blotting (WB) were used to measure the expression levels of USP46 and PHLPP1 in lung cancer tissue and adjacent normal tissue from lung cancer patients. The functional role of USP46 in regulating proliferation in lung cancer cells were examined by cell proliferation assay, radiation assay, genetic overexpression and knock down and chemical inhibition of relevant genes. The underlying mechanisms were investigated in multiple lung cancer cell line models by co-immunoprecipitation and ubiquitination assays. Results: This study identified strong downregulation of USP46 and PHLPP1 expression in lung cancer tissues relative to normal adjacent tissues. USP46 was further shown to inhibit lung cancer cell proliferation under normal growth conditions and during radiation induced DNA damage by antagonizing the ubiquitination of PHLPP1 resulting in the inhibition of AKT signaling. The effect of USP46 knock down on lung cancer cell proliferation was significantly reversed by exposure to radiation and AKT inhibition. Conclusions: USP46 is down-regulated in lung cancer, and it suppresses proliferation of lung cancer cells by inhibiting PHLPP1/AKT pathway. AKT inhibition slows proliferation of USP46 down-regulated lung cancer cells exposed to radiation suggesting a potential therapeutic avenue for USP46 down-regulated lung cancer through a combination of radiation and AKT inhibitor treatment.

Download Full-text

Long noncoding RNA UCA1 facilitates cell proliferation and inhibits apoptosis via activating PI3K/Akt pathway in retinoblastoma

10.21203/rs.2.15311/v1 ◽

2019 ◽

Author(s):

Zhongfang Yuan ◽

Zhaona Li

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Apoptosis ◽

Noncoding Rna ◽

Cell Counting ◽

Akt Pathway ◽

Promote Cell Proliferation ◽

Cell Clones ◽

Y79 Cells ◽

The Relationship

Abstract Background This study aimed to explored the effect of lncRNA-UCA1 on retinoblastoma (RB) and its potential molecular mechanisms.Methods In our study, the expression of lncRNA-UCA1 was measured by qRT-RCR in both RB tissues and RB HXO-RB44 and Y79 cells. The relationship between lncRNA-UCA1 expression and clinical parameters in RB patients were evaluated. Cell proliferation, cell clones, apoptosis and cell cycle of HXO-RB44 and Y79 cells were measured by cell counting kit-8 (CCK-8) assay, colony formation assay and flow cytometry, respectively. In addition, the expressions of PCNA, Caspase-3, survivin, p16, p21, CDK2, PI3K, p-PI3K, Akt, p-Akt and S6k in HXO-RB44 and Y79 cells were measured by western blot.Results lncRNA-UCA1 was highly expressed in both RB tissues and RB HXO-RB44 and Y79 cells. Moreover, the expression of lncRNA-UCA1 in RB patients was remarkedly correlated with tumor size, optic nerve invasion and pathologic grade. lncRNA-UCA1 markedly facilitated cell proliferation and cell cycle procession, as well as inhibited cell apoptosis in HXO-RB44 and Y79 cells. lncRNA-UCA1 dramatically increased the expression of S6k and the phosphorylation of PI3K and Akt in RB cells. LY294002 (PI3K inhibitor) reversed the effects of lncRNA-UCA1 on RB cell proliferation, apoptosis and cell cycle procession.Conclusions Our study indicated that lncRNA-UCA1 could promote cell proliferation and cell cycle procession, as well as inhibit cell apoptosis in RB via activating PI3K/Akt pathway.

Download Full-text

ZBTB7A, A Potential Biomarker for Prognosis and Immune Infiltrates, Inhibits Progression of Endometrial Cancer Based on Bioinformatics Analysis and Experiments

10.21203/rs.3.rs-63208/v1 ◽

2020 ◽

Author(s):

Rong Geng ◽

Yuhua Zheng ◽

Donghua Zhou ◽

Qingdong Li ◽

Ruiman Li ◽

...

Keyword(s):

Cell Proliferation ◽

Zinc Finger Protein ◽

Immune Cell ◽

Vital Role ◽

Marker Genes ◽

Potential Biomarker ◽

And Migration ◽

The Relationship

Abstract Backgroud: ZBTB protein is an important member of the C2H2 zinc finger protein family. As a transcription factor, it is widely involved in the transcriptional regulation of genes, cell proliferation, differentiation, and apoptosis. However, the role of ZBTB7A in uterine corpus endometrial carcinoma (UCEC) is unclear.Methods: In our work, we assessed the importance of ZBTB 7A in UCEC. Firstly, Using Oncomine and Tumor Immunoassay Resource (TIMER) databases to evaluate the expression of ZBTB7A. Secondly, we explored the co expression network of ZBTB7A through the cBioPortal online tool, Metascape, and LinkedOmics. TIMER was also used to explore the relationship between ZB TB7A and tumor immu ne invasion, and to detect the correlation between the ZBTB7A and the marker genes related to immune infiltration. Finally, CKK8,migration, ChIP assays were introduced to partly validate ZBTB7A function in endometrialcancer cells.Results: We found t he ZBTB7A expression in TIMER was associated with various cancers, especially UCEC. The decreased expre ssion of ZBTB7A was markedly related to the stage and prognosis of UCEC. Furthermore, ZBTB7A was also related to the expression of various immune markers s uch as Neutrophils, Dendritic cell, T cell (general), Th1, Th2, and Finally, we verified that ZBTB7 A repressed E2F4 transcription and inhibited cell s proliferation and migration . These results indicate that ZBTB7A may play a vital role in regulating immune cellinfiltration in UCEC, and is a valuable prognostic marker.Conclusions:In summary, we demonstrate that ZBTB7A is notably downregulated in UCEC, play s a vital role in regu lating immune cell infiltration, possesses diagnostic and pr ognostic values and attenuated E2F4 transcription and cell proliferation , migration in vitro.

Download Full-text

Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype

Journal of Clinical Pathology ◽

10.1136/jclinpath-2019-205778 ◽

2019 ◽

Vol 73 (3) ◽

pp. 139-146

Author(s):

Hao-Ran Li ◽

Bai-Quan Qiu ◽

Jian Gao ◽

Chun Jin ◽

Jia-Hao Jiang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Western Blot ◽

Blot Analysis ◽

Small Cell ◽

Small Cell Lung ◽

Invasion And Migration ◽

And Migration ◽

The Relationship

AimsTo unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC.MethodsImmunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods.ResultsElevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate.ConclusionsOur study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.

Download Full-text

MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

BMC Medical Genetics ◽

10.1186/s12881-020-0948-y ◽

2020 ◽

Vol 21 (1) ◽

Cited By ~ 2

Author(s):

Gan Xiaoling ◽

Liu Shuaibin ◽

Liang Kailu

Keyword(s):

Cell Proliferation ◽

Protein Expression ◽

Postmenopausal Osteoporosis ◽

Critical Role ◽

Dependent Manner ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

17Β Estradiol ◽

Dose Dependent

Abstract Background To investigated the role of miR-19b-3p in regulating bone marrow mesenchymal stem cell (BMSC) proliferation and osteoblast differentiation. Methods The expression of miR-19b-3p and lncRNA H19 were measured in postmenopausal osteoporosis patients and BMP-22 induced BMSCs using qRT-PCR. MiR-19b-3p mimic or inhibitor was transfected into BMP-2 induced BMSCs. Cell proliferation was measured by BrdU method. Protein expression of RUNX2 and COL1A1 were measured by western blot. PcDNA3.1-lncRNA H19 with or without miR-19b-3p mimic was transfected into BMP-2 induced BMSCs. Results The expression of miR-19b-3p was significantly up-regulated in postmenopausal osteoporosis patients and BMP-2 induced BMSCs. MiR-19b-3p overexpression dramatically elevated, while miR-19b-3p inhibition decreased cell proliferation of BMSCs. Additionally, protein expression levels of RUNX2 and COL1A1, as well as ALP activity were significantly promoted by miR-19b-3p mimic transfection and inhibited by miR-19b-3p inhibitor transfection. LncRNA H19 was obviously down-regulated in postmenopausal osteoporosis patients. H19 overexpression significantly decreased cell proliferation and differentiation by down-regulating miR-19b-3p. Moreover, the expression of miR-19b-3p was inhibited, while H19 elvated in 17β-estradiol (E2) treated BMSCs in a dose-dependent manner. Conclusion These data were the first to reveal the critical role of H19/miR-19b-3p in postmenopausal osteoporosis, and provided a new therapeutic target for OP.

Download Full-text

Long non-coding RNA LINC01116 acts as an oncogene in prostate cancer cells through regulation of miR-744-5p/UBE2L3 axis

Cancer Cell International ◽

10.1186/s12935-021-01843-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shengjie Yu ◽

Huihong Yu ◽

Yuanfeng Zhang ◽

Chuan Liu ◽

Weili Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Migration And Invasion ◽

Prostate Cancer Cells ◽

Cancer Cell Growth ◽

Non Coding Rna ◽

The Relationship ◽

Long Non Coding Rna

Abstract Background Long non-coding RNA (lncRNA) has been confirmed to exert a critical effect on the progression of tumors, including prostate cancer. Previous literature has demonstrated LINC01116 involves in activities of multiple cancers. However, the underlying role of LINC01116 in prostate cancer remains unclear. Methods qRT-PCR measured the expression of LINC01116 in prostate cancer cells. EdU experiment was used to detect cell proliferation. Transwell assays detected cell migration and invasion. Immunofluorescence staining and western blot assays were utilized to measure EMT progress. The binding relationship between RNAs was confirmed by a series of mechanism assays. In addition, rescue experiments were conducted to verify the relationship among RNAs. Results LINC01116 was found to be highly expressed in prostate cancer cells. Functional assays indicated that inhibition of LINC01116 could suppress cell proliferation, migration, invasion and EMT progress. Also, miR-744-5p was proven to bind with LINC01116. Moreover, UBE2L3 was verified as the target gene of miR-744-5p. In rescue assays, we discovered that inhibited miR-744-5p or overexpressed UBE2L3 could offset the suppressive influence of silencing LINC01116 on prostate cancer cells. Conclusion Our study suggested that lncRNA LINC01116 acted as an oncogene in prostate cancer and accelerated prostate cancer cell growth through regulating miR-744-5p/UBE2L3 axis.

Download Full-text