Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

You, Wei; Bi, Cheng; Liu, Xueqing; Xue, Shengjun; Qin, Hui; Jiang, Handong

doi:10.1038/s41598-017-00698-4

Cited by 37 publications

(28 citation statements)

References 37 publications

(45 reference statements)

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“…CCND1 has been postulated to play a potential oncogenic role in human cancers, including bladder cancer [34], estrogen receptor positive breast cancer [35] and prostate cancer [36]. Moreover, accumulating evidence has suggested that CCND1 has oncogenic potential in the development and progression of NSCLC [37][38][39]. In the present study, we firstly confirmed that CCND1 was a direct target of miR-342.…”

Section: Usa) Following the Manufactsupporting

confidence: 79%

Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 axis

Huang

Jin

et al. 2021

neo

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Puerarin has recently been demonstrated to play anti-cancer roles in a series of human cancers, including non-small cell lung cancer (NSCLC), possibly through regulation of cancer-related microRNAs (miRNAs). The purpose of the present study was to further investigate the detailed role and underlying mechanism of puerarin on NSCLC progression. Cell viability and apoptosis were assessed using the Cell Counting kit-8 (CCK-8) assay and flow cytometry, respectively. Transwell assays were performed to determine cell migration and invasion abilities. The qRT-PCR assay was employed to detect the expression of miR-342 and cyclin D1 (CCND1) mRNA, and CCND1 protein expression was evaluated by western blotting. The targeted interaction between miR-342 and CCND1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. We found that our data demonstrated that puerarin repressed cell viability, migration, invasion and cell cycle progression, and enhanced the apoptosis of NSCLC cells. miR-342 overexpression hindered the migration, invasion and cell cycle progression, and accelerated the apoptosis of NSCLC cells. miR-342 inhibited CCND1 expression by directly binding to the 3'-UTR of CCND1. Moreover, miR-342 overexpression-mediated anti-migration, anti-invasion, anti-cell cycle progression, and pro-apoptotic effects were abated by co-transfection of pcDNA-CCND1. More importantly, puerarin inhibited CCND1 expression by upregulating miR-342. Additionally, puerarinhampered NSCLC cell progression in vitro and tumor growth in vivo by upregulating miR-342. In conclusion, our study suggested that puerarin hampered NSCLC progression in vitro and in vivo at least partly through regulating miR-342/CCND1 axis, highlighting a novel mechanism of puerarin exerting anti-cancer property in NSCLC.

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Section: Usa) Following the Manufactsupporting

confidence: 79%

Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 axis

Huang

Jin

et al. 2021

neo

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“…Moreover, our study demonstrated that knockdown of FXR in colon cancer cells induced EMT, accompanied by upregulation of Snail, Slug, vimentin, fibronectin, and MMP-9, and downregulation of E-cadherin and ZO-1, whereas ectopic expression of FXR had reversed change. In non-small-cell lung cancer, FXR functions as a proto-oncogene, promoting cell proliferation by directly transactivating cyclin D1 46 . In pancreatic cancer, increased FXR promotes cell invasive and migratory ability 47 .…”

Section: Discussionmentioning

confidence: 99%

Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis

Guo

et al. 2020

Cell Death Dis

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Farnesoid X receptor (FXR, encoded by NR1H4), a critical regulator of bile acid homeostasis, is widely implicated in human tumorigenesis. However, the functional role of FXR in colorectal cancer (CRC) and the precise molecular mechanism remain unclear. In this study, we demonstrated that FXR expression was downregulated in colon cancer tissues and decreased expression of FXR predicted a poor prognosis. Knockdown of FXR promoted colon cancer cell growth and invasion in vitro, and facilitated xenograft tumor formation and distant metastasis in vivo, whereas ectopic expression of FXR had the reserved change. Mechanistic studies indicated that FXR exerted its tumor suppressor functions by antagonizing Wnt/β-catenin signaling. Furthermore, we identified an FXR/β-catenin interaction in colon cancer cells. The FXR/β-catenin interaction impaired β-catenin/TCF4 complex formation. In addition, our study suggested a reciprocal relationship between FXR and β-catenin, since loss of β-catenin increased the transcriptional activation of SHP by FXR. Altogether, these data indicated that FXR functions a tumor-suppressor role in CRC by antagonizing Wnt/β-catenin signaling.

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“…In breast carcinoma patients, the expression levels of FXR were positively correlated with tumor size and the proliferative rate of tumor cells [ 107 ], suggesting FXR as a prognosticator of invasive breast carcinoma. Consistently, the FXR expression was significantly increased in non-small cell lung cancer (NSCLC), which stimulated tumor growth through the direct transactivation of the cyclin D1 ( CCND1 ) gene [ 108 ]. Therefore, FXR may have pleiotropic effects on tumorigenesis, according to tissue types; FXR may primarily act as a tumor suppressor gene in enterohepatic tissues, but it can be a proto-oncogene in other tissues, including breast and lung.…”

Section: Biological Roles Of Fxr In Various Organs and The Inter-omentioning

confidence: 99%

Update on FXR Biology: Promising Therapeutic Target?

Han

2018

IJMS

151

108

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Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

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Farnesoid X receptor, a novel proto-oncogene in non-small cell lung cancer, promotes tumor growth via directly transactivating CCND1

Cited by 37 publications

References 37 publications

Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 axis

Puerarin alleviates the progression of non-small cell lung cancer by regulating the miR-342/CCND1 axis

Farnesoid X receptor antagonizes Wnt/β-catenin signaling in colorectal tumorigenesis

Update on FXR Biology: Promising Therapeutic Target?

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