Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women

Chung, Tony K.H.; Cheung, Tak Hong; Huen, Ngar Yee; Wong, Katherine W.Y.; Lo, Kwok-Tung; Yim, So Fan; Siu, Nelson S.S.; Wong, Yin Mei; Tsang, Po Ting; Pang, MF; Yu, Mei; To, Ka Fei; Mok, Samuel C.; Wang, Vivian W.; Li, Chen; Cheung, Albert Y.; Doran, Graeme; Birrer, Michael J.; Smith, Jeremy C.; Wong, Yick Fu

doi:10.1002/ijc.24071

Cited by 142 publications

(148 citation statements)

References 35 publications

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“…10 RNA quantity and quality were assessed with NanoDrop ND-1000 (Thermo Fisher Scientific). A 260 /A 280 nm !…”

Section: Rna Isolationmentioning

confidence: 99%

“…10 For mRNA quantification, total RNA (5 lg) was reverse transcribed using SuperScript II Reverse Transcriptase (Invitrogen) as instructed. qRT-PCR was done according to the manufacturer's protocol.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

“…10 Monoclonal mouse FOXC1 antibody (Abnova) and monoclonal mouse b-actin antibody (Sigma) were applied. Western blot quantification was performed using ImageJ software (National Institutes of Health).…”

Section: Western Blottingmentioning

confidence: 99%

“…8,9 Our group has previously identified a substantial number of aberrant miRNAs in EEC in a small-scale screening of miRNAs. 10 However, distinctive miRNA signatures and miRNA-related functional mechanisms associated with EEC progression remain to be elucidated.…”

mentioning

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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“…10 RNA quantity and quality were assessed with NanoDrop ND-1000 (Thermo Fisher Scientific). A 260 /A 280 nm !…”

Section: Rna Isolationmentioning

confidence: 99%

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

mentioning

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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“…Furthermore, miR-205 was shown to be downregulated in advanced-stage PCa in our studies (Figure 1a and 1b) and to be down-regulated in metastatic PCa. 23 Chung et al 24 reported that the aberrant expression of miR-205 took place in advanced stages in endometrial cancer. In addition, previous studies have shown that the level of miR-205 was inversely correlated with PSA and tumor stage.…”

Section: Mir-205 Suppresses Tumor Growth In Vivomentioning

confidence: 99%

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

Wang¹,

Li²,

Feng³

et al. 2013

Asian J Androl

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The purpose of this study was to elucidate the molecular mechanisms of microRNA-205 (miR-205) as a tumor suppressor in prostate cancer (PCa). In the present study, microRNA microarray analysis suggested that the expression of miR-205 was significantly decreased in advanced PCa compared with early PCa. Real-time PCR analysis also indicated that miR-205 expression was significantly decreased in PCa tissues compared with non-cancerous tissues. Moreover, the expression of miR-205 has been demonstrated to be associated with the clinicopathological stage and total/free prostate-specific antigen (PSA) level of PCa. Functional analyses showed that both the overexpression of miR-205 and the knockdown of c-SRC in PCa cell lines could inhibit cell growth, colony formation, migration, invasion and the cell cycle as well as induce cell apoptosis in vitro. Furthermore, over-expressing miR-205 reduced tumorigenicity in vivo. Through a luciferase activity assay and Western blotting, c-SRC was identified as a target of miR-205 in cells. The overexpression of miR-205 suppressed c-SRC and its downstream signaling molecules, including FAK, p-FAK, ERK1/2 and p-ERK1/2, and attenuated cell proliferation, invasion and tumor growth.

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Membrane occupation and recognition nexus (MORN) motif controls protein localization and function

et al. 2022

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The membrane occupation and recognition nexus (MORN) motif was first defined in 2000, when it was identified in the junctophilin protein family. Dozens of studies have been published ever since, mainly focusing on the function of a given MORN motif-containing protein in parasites, plants or animal cells. Proteins with MORN motifs are not only expressed in most animal and plant cell types, but also significantly differ in their intracellular localization, suggesting that the MORN motifs may fulfill multiple physiological functions. Recent studies have found that MORN motif-containing proteins junctophilin-1/2 and MORN3 play a role in cardiac hypertrophy, skeletal muscle fiber stability and cancer. Hence, MORN motif-containing proteins may be exploited to develop improved treatments for various pathological conditions, such as cardiovascular diseases. Here, we review current research on MORN motif-containing proteins in different organisms and provide both ideas and approaches for follow-up exploration of their functions and applications.

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Dysregulated microRNAs and their predicted targets associated with endometrioid endometrial adenocarcinoma in Hong Kong women

Cited by 142 publications

References 35 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

miR-205 is frequently downregulated in prostate cancer and acts as a tumor suppressor by inhibiting tumor growth

Membrane occupation and recognition nexus (MORN) motif controls protein localization and function

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