scholarly journals Hypermethylation of DLG3 Promoter Upregulates RAC1 and Activates the PI3K/AKT Signaling Pathway to Promote Breast Cancer Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bingbing Liu ◽  
Yanning Xu ◽  
Lin Zhang ◽  
Xue Yang ◽  
Ling Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Biological Activities ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

Objective. This investigation aimed to figure out the relation between discs large homolog 3 (DLG3) expression and the progression and prognosis of breast cancer (BC). Methods. qRT-PCR was utilized for confirming DLG3 expression and RAC1 mRNA expression in BC tissues and cells. Subsequently, after overexpression or interference of DLG3, the changes of the biological activities of BC cells, including cell proliferation, migration, invasion, and apoptosis, were detected through CCK-8, colony formation assay, wound healing assay, transwell assay, and flow cytometry, respectively. Furthermore, western blotting was utilized to measure the protein expression of DLG3 and RAC1, as well as related proteins of epithelial-mesenchymal transition (EMT) and the PI3K/AKT signaling pathway. Results. At both cellular and tissue level in BC, DLG3 was downregulated and methylation level was upregulated; RAC1 showed an opposite change and was of a negative correlation with DLG3. In MCF-7 and HCC1937, we found that the upregulation of DLG3 could inhibit RAC1 expression as well as cell proliferation, invasion, migration, and EMT, while promoting apoptosis. Also, DLG3 inhibited the activation of the P13K/AKT pathway. Conclusion. Hypermethylation of DLG3 promoter upregulates RAC1 and activates the PI3K/AKT pathway, thus promoting BC progression. This conclusion provides ideas and experimental basis for improving and treating BC patients.

scholarly journals MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells

2020 ◽  
Vol 15 (1) ◽  
pp. 959-970
Author(s):  
Lianshun Cui ◽  
Meiyan Yu ◽  
Xinglei Cui
Keyword(s):  
Cell Proliferation ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Pathway ◽  
The Novel ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition

AbstractDiabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Increasing evidence suggests that microRNA-30c-5p (miR-30c-5p) participates in the pathogenesis of DN, but the mechanism has not been clearly understood. Therefore, this study aimed to investigate the biological role of miR-30c-5p in human DN progression in vitro. Compared with the controls, DN tissues and high glucose-induced HK-2 cells had significantly reduced miR-30c-5p levels, while ROCK2 expression was prominently elevated. Additionally, the miR-30c-5p mimic distinctly facilitated cell proliferation and blocked cell apoptosis and epithelial–mesenchymal transition (EMT). However, ROCK2 was a target gene of miR-30c-5p, and the effects of miR-30c-5p mimic on cell proliferation, apoptosis and EMT were reversed by ROCK2 upregulation in vitro. Furthermore, the pathogenesis of DN was regulated by the miR-30c-5p/ROCK2 axis via the PI3K/AKT pathway. MiR-30c-5p regulating cell proliferation, apoptosis and EMT through targeting ROCK2 via the PI3K/AKT pathway provides the novel potential target for clinical treatment of DN.

scholarly journals ERas regulates cell proliferation and epithelial–mesenchymal transition by affecting Erk/Akt signaling pathway in pancreatic cancer

Human Cell ◽  
2020 ◽  
Vol 33 (4) ◽  
pp. 1186-1196
Author(s):  
Yang Liu ◽  
Peng Qin ◽  
Rong Wu ◽  
Lianfang Du ◽  
Fan Li
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

Abstract Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial–mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.

Thidiazuron suppresses breast cancer progression via targeting miR-132 and miR-202-5p/PTEN axis mediated dysregulation of PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Hairul-Islam Ibrahim ◽  
Mohammad Bani Ismail ◽  
Rebai Ben Ammar ◽  
Emad Ahmed
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Akt Signaling ◽  
Breast Cancer Metastasis ◽  
Akt Signaling Pathway ◽  
Stressful Environment

Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.

scholarly journals Capicua homology protein inhibits the progression of gastric cancer through the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
LU GE ◽  
Chang-long Hu ◽  
Zheng-hui Ge ◽  
Chun-rong Wang ◽  
Li Qian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Western Blot ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Qrt Pcr

Abstract Purpose Capicua homolog protein (CIC) played a broad role in the development of cancer in humans, however, its role in the progression of gastric cancer (GC) specifically has been unclear. This study aimed to explore the expression of CIC and its potential clinical value in patients with GC. Methods The CIC levels in GC tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR). And the in-vitro effects of CIC expression in MGC-803 cells on their proliferation, invasion, and the progression of epithelial-mesenchymal transition were assessed by CCK-8 assays, Matrigel-invasion analysis, qRT-PCR and Western blot assays, separately. In addition, the effects of downregulation of CIC on the activation of PI3K/AKT signaling pathway were measured using Western-blot analysis. Results The results showed CIC levels were lower in GC tissues and GC cell lines, and these lower CIC levels were correlated with tumor differentiation, Helicobacter pylori infection, TNM stage, and patient survival. In addition, CIC overexpression could promote cell proliferation, invasion, and progression of epithelial-mesenchymal transition in MGC-803 cells. Notably, exotic expression of CIC inactivated the phosphoinositide 3-kinase/protein kinase B signaling pathway. Conclusions In conclusion, our finding suggested CIC could serve as a potential diagnostic and prognostic biomarker and a probable therapy target for GC.

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