Downregulation of miR-874-3p promotes chemotherapeutic resistance in colorectal cancer via inactivation of the Hippo signaling pathway

Colorectal cancer (CRC) is one of the most common malignant tumors affecting the digestive tract. Moreover, the invasion and metastasis of CRC are the main reason therapy is usually inefficient. Decreased intercellular adhesion and enhanced cell motility induced by epithelial-mesenchymal transition (EMT) provide the basic conditions for the invasion and metastasis of the epithelial tumor cells of CRC. The Jiedu Sangen Decoction (JSD) is a prescription that has been used for more than 50 years in the treatment of CRC in the Zhejiang Hospital of Traditional Chinese Medicine. The aim of this study was to investigate the mechanism of JSD-triggered inhibition of invasion and metastasis in colon cancer. In vitro, the EMT model of the SW480 cells was induced by using epithelial growth factor (50 ng/mL). In vivo, the murine model of liver metastasis was constructed by inoculating mice with the SW480 cells. The effects of JSD on cell migration, invasion, and proliferation were determined using the transwell assay and CCK-8 assay. Moreover, the proteins related to the EMT process and the Hippo signaling pathway in the cancerous tissues and cell lines were determined by western blotting and immunostaining. JSD could significantly inhibit the proliferation, migration, and invasion of CRC cells and reverse their EMT status (all, P < 0.05). Moreover, after intervention with JSD, the levels of E-Cadherin (E-cad) increased, whereas the expression levels of N-Cadherin (N-cad), Yes-associated protein (YAP), and the transcriptional coactivator with the PDZ-binding motif (TAZ) decreased in both the SW480 cells and the tumor tissues. In summary, JSD reversed EMT and inhibited the invasion and metastasis of CRC cells through the Hippo signaling pathway.

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ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer

Molecular Therapy — Oncolytics ◽

10.1016/j.omto.2019.01.002 ◽

2019 ◽

Vol 12 ◽

pp. 204-213 ◽

Cited By ~ 4

Author(s):

Xu Wang ◽

Di Sun ◽

Jiandong Tai ◽

Si Chen ◽

Sen Hong ◽

...

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Hippo Signaling ◽

Hippo Signaling Pathway

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Reconstruction of the genome-scale co-expression network for the Hippo signaling pathway in colorectal cancer

Computers in Biology and Medicine ◽

10.1016/j.compbiomed.2018.05.023 ◽

2018 ◽

Vol 99 ◽

pp. 76-84 ◽

Cited By ~ 4

Author(s):

Fariba Dehghanian ◽

Zohreh Hojati ◽

Nazanin Hosseinkhan ◽

Zaynab Mousavian ◽

Ali Masoudi-Nejad

Keyword(s):

Colorectal Cancer ◽

Signaling Pathway ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Genome Scale

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Hippo signaling pathway in mammals：a new therapeutic target for tumors

Hereditas (Beijing) ◽

10.3724/sp.j.1005.2012.00269 ◽

2012 ◽

Vol 34 (3) ◽

pp. 269-280 ◽

Cited By ~ 2

Author(s):

Chuan-Ming XU ◽

Fu-Sheng WAN

Keyword(s):

Signaling Pathway ◽

Therapeutic Target ◽

Hippo Signaling ◽

Hippo Signaling Pathway

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Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01830-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xuehui Wang ◽

Changle Ji ◽

Jiashu Hu ◽

Xiaochong Deng ◽

Wenfang Zheng ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Cell Lines ◽

Luciferase Reporter ◽

Circular Rnas ◽

Hippo Signaling ◽

Hippo Signaling Pathway ◽

Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

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Inhibition of Hippo Signaling Improves Skin Lesions in a Rosacea-Like Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22020931 ◽

2021 ◽

Vol 22 (2) ◽

pp. 931

Author(s):

Jihyun Lee ◽

Yujin Jung ◽

Seo won Jeong ◽

Ga Hee Jeong ◽

Gue Tae Moon ◽

...

Keyword(s):

Mouse Model ◽

Signaling Pathway ◽

Normal Skin ◽

Skin Lesions ◽

Hippo Signaling ◽

Vascular Endothelial ◽

Expression Levels ◽

Hippo Signaling Pathway ◽

Endothelial Growth Factor

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.

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