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Guangzhou, China

Wu Z.,Southern Medical University | Sun H.,Sun Yat Sen University | Zeng W.,Laura Biotech Co | He J.,Southern Medical University | Mao X.,Southern Medical University
PLoS ONE | Year: 2012

Forkhead box protein O1 (FOXO1), a key member of the FOXO family of transcription factors, acts as a tumor suppressor and has been associated with various key cellular functions, including cell growth, differentiation, apoptosis and angiogenesis. Therefore, it is puzzling why FOXO protein expression is downregulated in cancer cells. MicroRNAs, non-coding 20~22 nucleotide single-stranded RNAs, result in translational repression or degradation and gene silencing of their target genes, and significantly contribute to the regulation of gene expression. In the current study, we report that miR-370 expression was significantly upregulated in five prostate cancer cell lines, compared to normal prostatic epithelial (PrEC) cells. Ectopic expression of miR-370 induced proliferation and increased the anchorage-independent growth and colony formation ability of DU145 and LNCaP prostate cancer cells, while inhibition of miR-370 reduced proliferation, anchorage-independent growth and colony formation ability. Furthermore, upregulation of miR-370 promoted the entry of DU145 and LNCaP prostate cancer cells into the G1/S cell cycle transition, which was associated with downregulation of the cyclin-dependent kinase (CDK) inhibitors, p27Kip1 and p21Cip1, and upregulation of the cell-cycle regulator cyclin D1 mRNA. Additionally, we demonstrated that miR-370 can downregulate expression of FOXO1 by directly targeting the FOXO1 3′-untranslated region. Taken together, our results suggest that miR-370 plays an important role in the proliferation of human prostate cancer cells, by directly suppressing the tumor suppressor FOXO1. © 2012 Wu et al. Source

Peng X.,Sun Yat Sen University | Guo W.,Sun Yat Sen University | Liu T.,Laura Biotech Co | Wang X.,Sun Yat Sen University | And 10 more authors.
PLoS ONE | Year: 2011

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis. © 2011 Peng et al. Source

Zhao X.,Sun Yat Sen University | Li Z.,Sun Yat Sen University | He B.,PLA421 Hospital | Liu J.,Sun Yat Sen University | And 5 more authors.
OncoTargets and Therapy | Year: 2013

Background: Neuroblastoma (NB) is the most common solid extracranial tumor in children. However, the molecular mechanism and progression of NB is largely unknown, and unfortunately, the prognosis is poor. Src-associated in mitosis with a molecular weight of 68 kDa (Sam68) is associated with carcinogenesis and neuro-genesis. The present study aimed to investigate the clinical and prognostic significance of Sam68 in NB. Methods: The expression of Sam68 in immortalized normal epithelial cells, NB cell lines, and in four cases of paired NB tissue and adjacent normal tissue from the same patient was examined using Western blotting, reverse transcription-polymerase chain reaction (PCR) and real-time reverse transcription-PCR. The proliferation of NB cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, Sam68 protein expression was analyzed in 90 NB cases characterized as clinicopathological using immunohistochemistry. Statistical analyses were applied to evaluate the diagnostic value and associations of Sam68 with clinical parameters. Results: Western blotting and reverse transcription-PCR showed that the expression level of Sam68 was markedly higher in NB cell lines than in the immortalized normal epithelial cells at both messenger RNA and protein levels. The MTT assay revealed that Sam68 expression supported proliferation of NB cells. Sam68 expression levels were significantly up-regulated in tumor tissues in comparison to the matched adjacent normal tissues from the same patient. Sam68 protein level was positively correlated with clinical stage (P<0.001), tumor histology (P<0.001), and distant metastasis (P=0.029). Patients with higher Sam68 expression had shorter overall survival time, whereas those with lower tumor Sam68 expression had longer survival time. Conclusion: Our results suggest that Sam68 expression is associated with neuroblastoma progression and may represent a novel and valuable predictor for prognostic evaluation of neuroblastoma patients. © 2013 Zhao et al. This work is published by Dove Medical Press Limited. Source

Xia W.,Huazhong University of Science and Technology | Ma X.,Anhui Medical University | Li X.,Huazhong University of Science and Technology | Dong H.,Huazhong University of Science and Technology | And 3 more authors.
Oncology Reports | Year: 2015

Epithelial-to-mesenchymal transition (EMT) has been implicated as a dynamic cellular process in embryonic development and invasion of human cancers. Snail1 is a critical convergence hub in EMT regulation which transcriptionally represses E-cadherin expression. Currently, published data indicate that upregulation of Snail is mainly due to transcriptional activation and regulation of protein stability and cellular location. However, whether there is an alternative regulatory mechanism remains unclear. Our study showed that the expression of miR-153 was noticeably downregulated in hepatocellular carcinoma (HCC) cell lines and tissues, compared with normal liver epithelial cells (NLCs) and matched adjacent normal HCC tissues. Ectopic expression of miR-153 inhibited the migration and invasion ability of HCC cells, while suppression of miR-153 rescued this inhibitory effect. In addition, upregulation of miR-153 in HCC cells resulted in a decrease in epithelial markers, E-cadherin and α-catenin, and an increase in mesenchymal markers, N-cadherin and vimentin, and vice versa. Moreover, we demonstrated that miR-153 downregulated Snail expression by directly targeting the 3′-untranslated region (3′UTR) of Snail. Taken together, our results suggest that miR-153 plays a critical role in suppressing EMT and HCC progression by direct suppression of Snail expression. © 2015, Spandidos Publications. All rights reserved. Source

Wang L.,Guangdong Pharmaceutical University | Ouyang F.,Sun Yat Sen University | Liu X.,Guangdong Pharmaceutical University | Wu S.,State Key Laboratory of Oncology in South China | And 7 more authors.
Oncotarget | Year: 2016

CDGSH iron sulfur domain 2 (CISD2) is localized in the outer mitochondrial membrane and mediates mitochondrial integrity and lifespan in mammals, but its role in cancer is unknown. In the current study, we reported that CISD2 mRNA and protein expression levels were significantly upregulated in gastric cancer cells compared to normal gastric epithelial cells (P < 0.001). Immunohistochemical analysis of 261 paraffin-embedded archived gastric cancer tissues showed that high CISD2 expression was significantly associated with clinical stage, TNM classifications, venous invasion and lymphatic invasion. Univariate and multivariate analysis indicated that high CISD2 expression was an independent prognostic factor for poorer overall survival in the entire cohort. Overexpressing CISD2 promoted, while silencing CISD2 inhibited, the proliferation of gastric cancer cells. Furthermore, we found that silencing endogenous CISD2 also significantly inhibited the proliferation and tumorigenicity of MGC-803 and SGC-7901 cells not only in vitro but also in vivo in NOD/SCID mice (P < 0.05). Furthermore, we found that CISD2 affected cell proliferation and tumorigenicity of gastric cancer cells through mediating the G1-to-S phase transition. Moreover, we demonstrated that the pro-proliferative effect of CISD2 on gastric cancer cells was associated with downregulation of cyclin-dependent kinase inhibitor p21Cip1 and p27Kip1, and activation of AKT signaling. The findings of this study indicate that CISD2 may promote proliferation and tumorigenicity, potentially representing a novel prognostic marker for overall survival in gastric cancer. Source

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