scholarly journals miR-22-3p/PGC1β Suppresses Breast Cancer Cell Tumorigenesis via PPARγ

PPAR Research ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xuehui Wang ◽  
Zhilu Yao ◽  
Lin Fang

In this study, we found that miR-22-3p expression was decreased in breast cancer (BC) cell lines and tissues. Overexpression of miR-22-3p inhibited the proliferation and migration of BC cells in vitro and in vivo, while depletion of miR-22-3p exhibited the opposite effect. Importantly, miR-22-3p could directly target PGC1β and finally regulate the PPARγ pathway in BC. In conclusion, miR-22-3p/PGC1β suppresses BC cell tumorigenesis via PPARγ, which may become a potential biomarker and therapeutic target.

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yeying Fang ◽  
Fraser C. Henderson ◽  
Qiong Yi ◽  
Qianqian Lei ◽  
Yan Li ◽  
...  

Background.Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cellsin vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells.Methods.Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels.In vitroandin vivostudies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells.Results.We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with thein vitrodata, CXCL16 overexpression inhibited tumorigenesisin vivo.Conclusions.Cellular CXCL16 suppresses invasion and metastasis of breast cancer cellsin vitroand inhibits tumorigenesisin vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.


2021 ◽  
Vol 11 ◽  
Author(s):  
Chun Tang ◽  
Xuehui Wang ◽  
Changle Ji ◽  
Wenfang Zheng ◽  
Yunhe Yu ◽  
...  

In this study, we demonstrated that miR-640 is significantly downregulated in breast cancer (BC) tissues and cell lines. Overexpression of miR-640 inhibited the proliferation and migration of BC in vitro and in vivo, while depletion of miR-640 exhibited the opposite effect. Importantly, miR-640 could directly target Wnt7b, thereby regulating Wnt/β-catenin signaling pathway in BC. In conclusion, miR-640/Wnt7b suppresses BC cells tumorigenesis via Wnt/β-catenin signaling pathway, which might be novel targets for BC targeted therapy.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii101
Author(s):  
Christoph Kesseler ◽  
Julian Kahr ◽  
Natalie Waldt ◽  
Nele Stroscher ◽  
Josephine Liebig ◽  
...  

Abstract PURPOSE To evaluate the role of the small GTPases RhoA, Rac1 and Cdc42 in meningiomas as therapeutic targets and their interactions in meningiomas. EXPERIMENTAL DESIGN We analyzed expression of GTPases in human meningioma samples and meningioma cell lines of various WHO grades. Malignant IOMM-Lee meningioma cells were used to generate shRNA mediated knockdowns of GTPases RhoA, Rac1 or Cdc42 and to study knockdown effects on proliferation and migration, as well as analysis of cell morphology by confocal microscopy. The same tests were used to investigate effects of the two inhibitors Fasudil and EHT-1864 of malignant IOMM-Lee, KT21 and benign Ben-Men cells and the effects of these drugs on IOMM-Lee knockdown cells. The effects of GTPase knockdowns and Fasudil treatment were studied in terms of overall survival by intracranial xenografts of mice. Potential interactions of GTPases regarding NF2, mTOR and FAK-Paxillin were examined. RESULTS Small GTPases were upregulated in meningiomas of higher tumor grades. Reduced proliferation and migration could be achieved by GTPase knockdown in IOMM-Lee cells. Additionally, the ROCK-inhibitor Fasudil and Rac1-inhibitor EHT-1864 reduced proliferation in different meningioma cell lines and reduced proliferation and migration independent of GTPase knockdowns/status. Moreover, overall survival in vivo could also be increased by knockdowns of RhoA and Rac1 as well as Fasudil treatment. GTPase expression was affected dependent on the NF2 status but effects were not very distinct, indicating that NF2 is not strongly involved in GTPase regulation in meningiomas. In terms of mTOR and FAK-Paxillin signaling, each GTPase changes those pathways in a different manner. CONCLUSION Small GTPases are important effectors in meningioma proliferation and migration in vitro as well as survival in vivo and their inhibition should be considered as potential treatment option.


2011 ◽  
Vol 63 (2) ◽  
pp. 264-271 ◽  
Author(s):  
Gopal Singh ◽  
Argun Akcakanat ◽  
Chandeshwar Sharma ◽  
David Luyimbazi ◽  
Katherine Naff ◽  
...  

2021 ◽  
Author(s):  
Saima Najm ◽  
Humaira Naureen ◽  
Fareeha Anwar ◽  
Muhammad Mubbashir Khan ◽  
Rabia Ali

Abstract Background and objectives: Breast cancer presents high morbidity among women with various treatment challenges. This study aims to evaluate the repurposed lamotrigine schiff base metal (LTG-SB-M) coordinates against in-vitro MCF-7 breast cancer cell lines and in-vivo N-methylnitrosourea (NMU)-persuaded toxicity of rats’ mammary gland. Method: In-silico computational analysis and in vitro cytotoxic studies on MCF-7 breast cancer cell lines was executed to build up the assumptions. In-vivo NMU-induced anticancer potential was assessed in forty Wistar rats; assigned into five groups of 8 rats each. Group I served as normal control and received normal saline, Group II received NMU (50 mg/kg), Group III received tamoxifen, whereas; Group IV and V received LTG-SB-M derivative (LAC3, LBC3) at dose of 100 mg/kg body weight, for 15 consecutive days. Intraperitoneal injection of NMU (single dose) was given at the age of 5, 9 and 13 weeks to the rats with the three week interval. For all experimental animals; biochemical markers were assessed. DNA strand breakage alongside the hormonal profile of estrogen and progesterone was also estimated. Results: All tested compounds present significant activity against MCF-7 cell lines in vitro and NMU-induced mammary tumor in vivo. The in vivo results of tested compounds present a significant decrease in weight of organ; with reinstated renal and hepatic enzymes. Histological analysis revealed strong countenance of proteins, estrogen, and progesterone in NMU-treated rats. Conclusion: These results suggest that LTG-SB-M complex can be used as better anticancer agent against breast cancer.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3430
Author(s):  
Chifei Kang ◽  
Ran Rostoker ◽  
Sarit Ben-Shumel ◽  
Rola Rashed ◽  
James Andrew Duty ◽  
...  

TMEM176B is a member of the membrane spanning 4-domains (MS4) family of transmembrane proteins, and a putative ion channel that is expressed in immune cells and certain cancers. We aimed to understand the role of TMEM176B in cancer cell signaling, gene expression, cell proliferation, and migration in vitro, as well as tumor growth in vivo. We generated breast cancer cell lines with overexpressed and silenced TMEM176B, and a therapeutic antibody targeting TMEM176B. Proliferation and migration assays were performed in vitro, and tumor growth was evaluated in vivo. We performed gene expression and Western blot analyses to identify the most differentially regulated genes and signaling pathways in cells with TMEM176B overexpression and silencing. Silencing TMEM176B or inhibiting it with a therapeutic antibody impaired cell proliferation, while overexpression increased proliferation in vitro. Syngeneic and xenograft tumor studies revealed the attenuated growth of tumors with TMEM176B gene silencing compared with controls. We found that the AKT/mTOR signaling pathway was activated or repressed in cells overexpressing or silenced for TMEM176B, respectively. Overall, our results suggest that TMEM176B expression in breast cancer cells regulates key signaling pathways and genes that contribute to cancer cell growth and progression, and is a potential target for therapeutic antibodies.


SpringerPlus ◽  
2014 ◽  
Vol 3 (1) ◽  
pp. 417 ◽  
Author(s):  
Masato Terashima ◽  
Kazuko Sakai ◽  
Yosuke Togashi ◽  
Hidetoshi Hayashi ◽  
Marco A De Velasco ◽  
...  

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