Tissue Transglutaminase Impairs HTR-8/SVneo Trophoblast Cell Invasion via the PI3K/AKT Signaling Pathway

2021 ◽  
pp. 1-9
Author(s):  
Mi Cheng ◽  
Zequn Liu ◽  
Wanqing Ji ◽  
Jie Zheng ◽  
Huiqian Zeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Tissue Transglutaminase ◽  
Akt Signaling ◽  
Trophoblast Invasion ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
Phosphorylated Akt ◽  
Proliferation And Invasion

<b><i>Objectives:</i></b> The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE. <b><i>Methods:</i></b> HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR. <b><i>Results:</i></b> tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoted apoptosis. In addition, upregulation of tTG induced an increase of PI3K and phosphorylated AKT and a decrease of MMP-2 and MMP-9 expression. tTG-knockdown significantly promoted the proliferation and invasion of HTR-8/SVneo cells and inhibited the apoptosis. Furthermore, the PI3K expression level was reduced, and the MMP-2/MMP-9 protein levels were increased. <b><i>Conclusion:</i></b> Taken together, the present study demonstrated that tTG-overexpression inhibited HTR-8/SVneo cell invasion via reducing the expression of MMP-2 and MMP-9 by activating PI3K/AKT signaling pathway, which may lead to the occurrence or development of PE. The present data provide new insights into modulation of tTG expression as a potential therapeutic target for PE.

scholarly journals GSK2126458 has the potential to inhibit the proliferation of pancreatic cancer uncovered by bioinformatics analysis and pharmacological experiments

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yueqin Feng ◽  
Yuguan Jiang ◽  
Fengjin Hao
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Inhibitors ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Hub Genes ◽  
Pancreatic Cancer Cells ◽  
Proliferation And Invasion

Abstract Background Pancreatic cancer is one of the most serious digestive malignancies. At present, there is an extreme lack of effective strategies in clinical treatment. The purpose of this study is to identify key genes and pathways in the development of pancreatic cancer and provide targets for the treatment of pancreatic cancer. Methods GSE15471 and GSE62165 were used to screen differentially expressed genes by GEO2R tool. Hub genes prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The drug susceptibility data of pan-cancer cell lines is provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). Finally, the effects of PI3K–Akt signaling pathway inhibitors on cell viability of pancreatic cancer cells were detected by cell proliferation and invasion assays. Results A total of 609 differentially expressed genes were screened and enriched in the focal adhesion, phagosome and PI3K–Akt signaling pathway. Of the 15 hub genes we found, four were primarily associated with the PI3K–Akt signaling pathway, including COL3A1, EGF, FN1 and ITGA2. GDSC analysis showed that mTOR inhibitors are very sensitive to pancreatic cancer cells with mutations in EWSR1.FLI1 and RNF43. Cell proliferation and invasion results showed that mTOR inhibitors (GSK2126458) can inhibit the proliferation of pancreatic cancer cells. Conclusions This study suggested that the PI3K–Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer.

Ginsenoside-Rg5 Inhibits Retinoblastoma Proliferation and Induces Apoptosis through Suppressing BCL2 Expression

Chemotherapy ◽  
2018 ◽  
Vol 63 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Yong Cui ◽  
Yan Su ◽  
Liya Deng ◽  
Wenjing Wang
Keyword(s):  
Cell Proliferation ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Mrna Levels ◽  
Akt Signaling Pathway ◽  
Retinoblastoma Cells ◽  
Anti Cancer ◽  
Ginsenoside Rg5 ◽  
Bcl2 Expression

Background/Aims: Although the cure rate for retinoblastoma is high, surviving patients are at risk for developing secondary cancers and require life-long follow-up. It is imperative to discover and develop novel therapeutic agents with better efficiency and fewer adverse effects. Ginsenoside-Rg5 is an active derivate from ginseng and exerts anti-cancer activity in breast cancer cells. However, it is still unclear whether ginsenoside-Rg5 has similar anti-cancer functions in retinoblastoma. Methods: Retinoblastoma cells were treated with ginsenoside-Rg5, followed by MTT assay analysis of the cell viability, cell number assay and colony formation assay analyses of cell proliferation, and flow cytometric analysis of apoptosis. Gene mRNA levels and protein levels were determined by quantitative real-time PCR and Western blot, respectively. Results: Ginsenoside-Rg5 inhibited retinoblastoma cell viability in a dose-dependent and time-dependent manner via preventing cell proliferation and inducing cell apoptosis. BCL2 expression was downregulated by ginsenoside-Rg5 treatment via inactivating the AKT signaling pathway. BCL2 overexpression completely eliminated the inhibitory effect of ginsenoside-Rg5 on cancer cell viability. Conclusion: Ginsenoside-Rg5 inhibits cell proliferation and induces apoptosis in retinoblastoma cells by inactivating the AKT signaling pathway, thereby downregulating BCL2 expression.

scholarly journals TUSC3 inhibits cell proliferation and invasion in cervical squamous cell carcinoma via suppression of the AKT signaling pathway

2021 ◽  
Author(s):  
Fei Sun ◽  
Qiuling Jie ◽  
Qi Li ◽  
Yunjian Wei ◽  
Ping Long ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cervical Squamous Cell Carcinoma ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Proliferation And Invasion

Abstract Background The expression of tumor suppressor candidate 3 (TUSC3) is associated with proliferation in several types of cancer, leading to an unfavorable prognosis. The present study aimed to assess the cellular and molecular function of TUSC3 in patients with cervical squamous cell carcinoma (CSCC). Methods Levels of mRNA expressions of TUSC3 were analyzed in CSCC tissues and six cell lines using qRT-PCR. Immunohistochemistry(IHC) was used to evaluate the protein expression level of TUSC3 in four paired specimens, 220 paraffin-embedded CSCC specimens and 60 cases of normal cervical tissues(NCTs), respectively. Short hairpin RNA interference was employed for TUSC3 knockdown. Cell proliferation, migration and invasion was evaluated using growth curve, MTT assay, wound healing and transwell assay respectively. Results The results demonstrated that TUSC3 mRNA and protein expression levels were down-regulated in CSCC samples. Multivariate and univariate analyses indicated that TUSC3 was an independent prognostic factor for patients with CSCC. Decreased TUSC3 expression levels were significantly associated with proliferation and an aggressive phenotype of cervical cancer cells. Moreover, the knockdown of TUSC3 promoted migration and invasion of cancer cells, while the increased expression of TUSC3 exhibited the opposite effects. The down-regulation of TUSC3 facilitated proliferation and invasion of CSCC cells through the activation of the AKT signaling pathway. Conclusions Our data demonstrated that the down-regulation of TUSC3 promoted CSCC cell metastasis via the AKT signaling pathway. Therefore, TUSC3 may serve as a novel prognostic marker and potential target for CSCC.

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