MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer

Ibrahim, Fateen Farhana; Jamal, Rahman; Syafruddin, Saiful Effendi; Mutalib, Nurul Syakima Ab; Saidin, Sazuita; MdZin, Reena; Mollah, Mohammad Manir Hossain; Mokhtar, Norfilza Mohd

doi:10.1186/s13048-015-0186-7

Cited by 51 publications

(47 citation statements)

References 37 publications

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“…In contrast to epithelial cancer cells where miR-200c expression blocks EMT, proliferation, and metastasis (Gregory et al, 2008;Hur et al, 2013;Ibrahim et al, 2015;Liu et al, 2014;Song et al, 2015;Tang et al, 2013;Yu et al, 2010), our analysis of osteosarcoma tumors indicate a robust correlation between miR-200c expression and metastasis. To further test this novel paradigm, we performed a series of in vitro experiments with U2-OS cells, a human cell line originally derived from a primary osteosarcoma.…”

Section: Exogenous Expression Of Mir-200c In Osteosarcoma Cells Enhancontrasting

confidence: 67%

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

et al. 2016

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Lung metastasis is the major cause of death in osteosarcoma patients. However, molecular mechanisms underlying this metastasis remain poorly understood. To identify key molecules related with pulmonary metastasis of pediatric osteosarcomas, we analyzed high‐throughput miRNA expression in a cohort of 11 primary tumors and 15 lung metastases. Results were further validated with an independent cohort of 10 primary tumors and 6 metastases. In parallel, we performed immunohistochemical analysis of activated signaling pathways in 36 primary osteosarcomas. Only phospho‐AKT associated with lower overall survival in primary tumors, supporting its role in osteosarcoma progression. CTNNB1 expression also associated with lower overall survival but was not strong enough to be considered an independent variable. Interestingly, miR‐200c was overexpressed in lung metastases, implicating an inhibitory feed‐back loop to PI3K‐AKT. Moreover, transfection of miR200c‐mimic in U2‐OS cells reduced phospho‐AKT levels but increased cellular migration and proliferation. Notably, miR‐200c expression strongly correlated with miR‐141 and with the osteogenic inhibitor miR‐375, all implicated in epithelial to mesenchymal transition. These findings contrast epithelial tumors where reduced miR‐200c expression promotes metastasis. Indeed, we noted that osteosarcoma cells in the lung also expressed the epithelial marker CDH1, revealing a change in their mesenchymal phenotype. We propose that miR‐200c upregulation occurs late in osteosarcoma progression to provide cells with an epithelial phenotype that facilitates their integration in the metastatic lung niche. Thus, our findings identify phospho‐AKT in the primary tumor and miR‐200c later during tumor progression as prognostic molecules and potential therapeutic targets to prevent progression and metastasis of pediatric osteosarcomas.

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Section: Exogenous Expression Of Mir-200c In Osteosarcoma Cells Enhancontrasting

confidence: 67%

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

et al. 2016

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“…Another validated target of miR-200c is DLC1 (deleted in liver cancer-1), which is a tumor and metastasis suppressor that regulates actin formation and focal adhesion (Feng et al, 2013). In a study on EOC, forced expression of miR-200c reduced DLC1 expression in conjunction with increased cell proliferation and suppression of serous EOC invasion and migration (Ibrahim et al, 2015), consistent with the known role of DLC1 .…”

Section: Mir-200c-mediated Metastasissupporting

confidence: 52%

miR-200c Regulation of Metastases in Ovarian Cancer: Potential Role in Epithelial and Mesenchymal Transition

2016

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Among the gynecological malignancies, ovarian cancer is the most fatal due to its high mortality rate. Most of the identified cases are epithelial ovarian cancer (EOC) with five distinct subtypes: high-grade serous carcinoma, low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, and clear-cell carcinoma. Lack of an early diagnostic approach, high incidence of tumor relapse and the heterogenous characteristics between each EOC subtypes contribute to the difficulties in developing precise intervention and therapy for the patients. MicroRNAs (miRNAs) are single-stranded RNAs that have been shown to function as tumor suppressors or oncomiRs. The miR-200 family, especially miR-200c, has been shown to be implicated in the metastasis and invasion of ovarian carcinoma due to its functional regulation of epithelial-to-mesenchymal transition (EMT). This mini review is aimed to summarize the recent findings of the miR-200c functional role as well as its validated targets in the metastasis cascade of ovarian cancer, with a focus on EMT regulation. The potential of this miRNA in early diagnosis and its dual expression status are also discussed.

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“…Since miR-122 has been identified as a marker of differentiation [94, 95] it makes sense that this miRNA is decreased in CCA as opposed to PSC. In contrast to miR-122 levels, miR-200c is downregulated in PSC but upregulated in CCA, and previous work has shown that miR-200c increases tumor growth and proliferation [96, 97], helping to explain this discrepancy in expression. Finally, miR-92a, another miRNA that supports tumor growth [98], shows decreased expression in PBC but increased expression in BA.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

et al. 2017

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Cholangiopathies are a group of rare, devastating diseases that arise from damaged cholangiocytes, the cells that line the intra- and extra-hepatic bile ducts of the biliary epithelium. Cholangiopathies result in significant morbidity and mortality and are a major cause of liver transplantation. A better understanding of the underlying pathogenesis that influences cholangiocyte dysregulation and cholangiopathy progression is necessary, considering the dismal prognosis associated with these diseases. MicroRNAs are a class of small, non-coding RNAs that regulate post-transcriptional mRNA expression of specific genes. The role of microRNAs has expanded to include the initiation and development of many diseases, including cholangiopathies. Understanding microRNA regulation of cholangiopathies may provide diagnostic and therapeutic benefit for these diseases. In this review, the authors primarily focus on studies published within the last five years that help determine the diagnostic and therapeutic potential of microRNAs in cholangiopathies.

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MicroRNA-200c and microRNA-31 regulate proliferation, colony formation, migration and invasion in serous ovarian cancer

Cited by 51 publications

References 37 publications

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

miR‐200c and phospho‐AKT as prognostic factors and mediators of osteosarcoma progression and lung metastasis

miR-200c Regulation of Metastases in Ovarian Cancer: Potential Role in Epithelial and Mesenchymal Transition

Diagnostic and therapeutic potentials of microRNAs in cholangiopathies

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