Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

Wong, Yick Fu; Cheung, Tak Hong; Lo, Kwok Wai; Yim, So Fan; Siu, Nelson S.S.; Chan, Samuel C.S.; Ho, Tina W.F.; Wong, Kenneth; Yu, Mei; Wang, V W; Li, C; Gardner, Ginger J.; Bonome, Tomás; Johnson, William B.; Smith, Jeremy C.; Chung, Tony K.H.; Birrer, Michael J.

doi:10.1038/sj.onc.1209986

Cited by 108 publications

(87 citation statements)

References 62 publications

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“…6). 13 Based on our qRT-PCR detection and correlation analysis, miR-204 and FOXC1 expressions were inversely related in EECs.…”

Section: Foxc1 Is a Target For Mir-204mentioning

confidence: 93%

“…13 To designate potential target genes for miR-204, each of these gene sequences was aligned with the miR-204 sequence using miRBase (http://www.microrna.org) and TargetScan (http://www.targetscan.org). Interestingly, we found two miR-204 potential binding sites at the FOXC1 3 0 UTR named BS1 and BS2 (Fig.…”

Section: Foxc1 Is a Target For Mir-204mentioning

confidence: 99%

“…23 Family members including FOXA1, FOXC1, FOXO1 and FOXP1 were found to be aberrantly expressed in EEC. 13,24,25 miRBase and TargetScan databases predict these FOX genes to be potentially targeted by 11/16 dysregulated miRNAs (miR-7, miR-9, miR135b, miR-183, miR-199b, miR-204, miR-205, miR-223, miR-449, miR-449b and miR-494) retrieved from our profiling data. Among 4 cancer progression-and metastasis-related miRNAs we identified, miR-7, miR-449b and miR-204 target FOX genes concurrently.…”

Section: Cancer Cell Biologymentioning

confidence: 99%

“…Among 4 cancer progression-and metastasis-related miRNAs we identified, miR-7, miR-449b and miR-204 target FOX genes concurrently. As FOX genes are involved in progression and metastasis of various cancers 23 including EEC, 10,13,24 this provided the basis for focusing further investigation on FOX genes. Our study confirmed miR-204 directly targets FOXC1 3 0 UTR, and overexpression of miR-204 diminishes FOXC1 mRNA and protein expressions in endometrioid-type endometrial cancer cell line, HEC1A.…”

Section: Cancer Cell Biologymentioning

confidence: 99%

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Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Chung

Lau

Cheung

et al. 2011

Intl Journal of Cancer

152

128

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TXMicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3 0 -untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression-and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.Endometrial cancer is a common cause of gynecological cancer death. The most dominant subtype, endometrioid endometrial cancer (EEC), accounts for >80% of this cancer. Menopause and unopposed estrogenic stimulation are typical risk factors. Patients are generally treated with surgery, radiation, chemotherapy or hormone therapy. Patients with early stage disease have 5-year survival rates over 80%, however, about 15-20% develop metastasis. 1 These patients and those with advanced stage disease or recurrence have poor prognosis due to limitation of effective treatment. 2 Understanding the pathogenesis of this disease may provide insights for the development of novel therapeutic strategies.MicroRNAs (miRNAs) are small noncoding RNA molecules of 19-24 nucleotides that regulate gene expression posttranscriptionally through imperfect base pairing with the 3 0 -untranslated region (3 0 UTR) of target mRNAs, causing transcript degradation and translational inhibition. 3 Approximately 20-30% of all genes are targeted by miRNAs and a single miRNA may target as many as 200 genes. 4 In human cancers, >50% of the miRNA genes are located in chromosomal fragile sites, minimal regions containing loss of heterozygosity, minimal amplicons or common breakpoint regions. 5 DNA ...

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“…6). 13 Based on our qRT-PCR detection and correlation analysis, miR-204 and FOXC1 expressions were inversely related in EECs.…”

Section: Foxc1 Is a Target For Mir-204mentioning

confidence: 93%

Section: Foxc1 Is a Target For Mir-204mentioning

confidence: 99%

Section: Cancer Cell Biologymentioning

confidence: 99%

Section: Cancer Cell Biologymentioning

confidence: 99%

See 2 more Smart Citations

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Chung

Lau

Cheung

et al. 2011

Intl Journal of Cancer

152

128

View full text Add to dashboard Cite

show abstract

“…IL8 expression was associated with increased metastatic potential (Berry et al 2001) and increased angiogenesis in endometrial tumours, as measured by microvascular density counts (Fujimoto et al 2002). CXCL5 expression is also elevated in endometrial adenocarcinoma (Wong et al 2007), and may perform similar functions to IL8.…”

Section: Cytokines and Chemokinesmentioning

confidence: 98%

Inflammatory events in endometrial adenocarcinoma

Wallace

Gibson²,

Saunders

et al. 2010

Journal of Endocrinology

111

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Endometrial adenocarcinoma is the most common gynaecological malignancy in western countries. Many of the established risk factors for developing endometrial cancer are associated with excess exposure to oestrogen unopposed by progesterone. These include nulliparity, late onset of the menopause, post-menopausal hormone replacement therapy and obesity. However, a number of risk factors also promote inflammation, another feature proposed to influence cancer development. The human cycling endometrium undergoes regular and cyclical episodes of inflammation. Moreover, hormonal and genetic changes that occur early in the development of endometrial adenocarcinoma can exacerbate the local inflammatory environment. Via alterations in the expression of local mediators and immune cell function, these may contribute to the development of endometrial cancer. This review discusses the contribution of inflammation to the initiation and progression of endometrial adenocarcinoma. Manipulation of inflammatory pathways may therefore represent a therapeutic target in endometrial adenocarcinoma.

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CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

Zhang

Wang

Sun

et al. 2020

Cancer Communications

124

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The components of the tumor microenvironment (TME) in solid tumors, especially chemokines, are currently attracting much attention from scientists. C-X-C motif chemokine ligand 5 (CXCL5) is one of the important chemokines in TME. Overexpression of CXCL5 is closely related to the survival time, recurrence and metastasis of cancer patients. In TME, CXCL5 binds to its receptors, such as C-X-C motif chemokine receptor 2 (CXCR2), to participate in the recruitment of immune cells and promote angiogenesis, tumor growth, and metastasis. The CXCL5/CXCR2 axis can act as a bridge between tumor cells and host cells in TME. Blocking the transmission of CXCL5/CXCR2 signals can increase the sensitivity and effectiveness of immunotherapy and slow down tumor progression. CXCL5 and CXCR2 are also regarded as biomarkers for predicting prognosis and molecular targets for customizing the treatment. In this review, we summarized the current literature regarding the biological functions and clinical significance of CXCL5/CXCR2 axis in TME. The possibility to use CXCL5 and CXCR2 as potential prognostic biomarkers and therapeutic targets in cancer is also discussed

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Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

Cited by 108 publications

References 62 publications

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Inflammatory events in endometrial adenocarcinoma

CXCL5/CXCR2 axis in tumor microenvironment as potential diagnostic biomarker and therapeutic target

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