Knockdown of lncRNA H19 restores chemo-sensitivity in paclitaxel-resistant triple-negative breast cancer through triggering apoptosis and regulating Akt signaling pathway

2018 ◽  
Vol 359 ◽  
pp. 55-61 ◽  
Author(s):  
Jiguang Han ◽  
Baojuan Han ◽  
Xueya Wu ◽  
Jie Hao ◽  
Xiaoqun Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Akt Signaling ◽  
Akt Signaling Pathway

scholarly journals WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer

2018 ◽  
Vol 48 (5) ◽  
pp. 1968-1982 ◽  
Author(s):  
Hongming Song ◽  
Tianqi Wu ◽  
Dan Xie ◽  
Dengfeng Li ◽  
Kaiyao Hua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Signaling Pathway ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Qrt Pcr

Background/Aims: Dysregulated expression of WW domain-binding protein 2 (WBP2) is associated with poor prognosis in ER+ breast cancer patients. However, its role in triple negative breast cancer (TNBC) has not been previously assessed. Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells. Methods: qRT-PCR, western blotting, and immunohistochemical staining were used to evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA-MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR-613 mimics, or miR-613 inhibitors were subject to assays for cell viability, apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting or qRT-PCR were employed to monitor changes in signaling pathway-related genes and proteins. Luciferase assays were performed to assess whether WBP2 is a direct target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo using mouse xenograft models. Results: The expression of WBP2 was upregulated in TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67 in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to the 3’-untranslated region (3’-UTR) of WBP2 and regulated the expression of WBP2. Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by inhibition of miR-613. Conclusion: WBP2 overexpression is associated with the poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt signaling pathway.

scholarly journals GPRC5A Is a Negative Regulator of the Pro-Survival PI3K/Akt Signaling Pathway in Triple-Negative Breast Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Lu Yang ◽  
Shaorong Zhao ◽  
Tong Zhu ◽  
Jin Zhang
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Cell Apoptosis ◽  
Triple Negative ◽  
Akt Signaling ◽  
Breast Cancer Cell Lines ◽  
Akt Signaling Pathway

Breast cancer is one of the most common types of malignancy worldwide; however, its underlying mechanisms remain unclear. In the present study, we investigated the roles of G-protein-coupled receptor family C, member 5, group A (GPRC5A) in cell apoptosis in triple-negative breast cancer (TNBC). The expression of GPRC5A in breast cancer cell lines was detected by real time PCR and western blot. And the results suggested that GPRC5A was downregulated in breast cancer cell lines compared to normal breast epithelial cell lines. Additionally, the expression of GPRC5A in TCGA database was analyzed in silico. GPRC5A exhibited the lowest expression levels in TNBC compared to ER+ and HER2+ breast cancer. Overexpression of GPRC5A in MDA-MB-231 and MDA-MB-468 cells promoted apoptosis, whereas depletion of GPRC5A in T47D and MCF7 cells inhibited cell apoptosis via the intrinsic apoptotic pathway. We performed RNA-sequencing in GPRC5A overexpressed MDA-MB-231 and the control cells. The results facilitated the identification of a number of signaling pathways involved in this process, and the PI3K/Akt signaling pathway was found to be one the most important. A specific activator of the PI3K/Akt signaling pathway inhibited apoptosis of breast cancer cells, whereas cotreatment of this activator with a GPRC5A-expressing plasmid reduced this effect. Similarly, a specific inhibitor of the PI3K/Akt signaling pathway increased cell apoptosis by activating caspase-3 and caspase-9, whereas co-incubation of the inhibitor with a short hairpin RNA targeting GPRC5A significantly reduced the cell apoptotic rate. Additionally, the overexpression of GPRC5A suppressed tumor growth by inducing cell apoptosis in vivo. Taken together, the present study identified GPRC5A as a protective factor against the progression of human triple-negative breast cancer by increasing cell apoptosis via the regulation of the PI3K/Akt signaling pathway.

scholarly journals Entelon® (Vitis vinifera Seed Extract) Prevents Cancer Metastasis via the Downregulation of Interleukin-1 Alpha in Triple-Negative Breast Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3644
Author(s):  
Daeun You ◽  
Yisun Jeong ◽  
Sun Young Yoon ◽  
Sung A Kim ◽  
Eunji Lo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Cancer Metastasis ◽  
Triple Negative ◽  
Interleukin 1 ◽  
Metastatic Potential ◽  
Cancer Cell Proliferation ◽  
Dependent Pathway

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.

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