Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication

Misiewicz-Krzemińska, Irena; Sarasquete, María Eugenia; Quwaider, Dalia; Krzemiński, Patryk; Ticona, Fany Veronica; Paíno, Teresa; Delgado, Maria M.; Aires, Andreia; Ocio, Enrique M.; García‐Sanz, Ramón; Miguel, Jesús F. San; Gutiérrez, Norma C.

doi:10.3324/haematol.2012.070011

Cited by 71 publications

(65 citation statements)

References 45 publications

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“…A recent study demonstrated that p53 was the target gene of miR-214 (35). In the present study, a conservative miR-214 binding site in the 3'-UTR of p53 was detected using bioinformatics software programs.…”

Section: Discussionmentioning

confidence: 98%

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

Wang

et al. 2015

International Journal of Molecular Medicine

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Abstract. Breast cancer (BC) is the foremost cause of cancerrelated mortality in women worldwide. An increasing number of studies has confirmed that microRNAs (miRNAs or miRs) play an important role in the development and progression of BC. microRNA-214 (miR-214), a member of the miRNA family, has been demonstrated to function as both a tumor suppressor and oncogene in various types of human cancer. However, the biological function of miR-214 in BC remains unclear. The present study was designed to investigate the potential role of miR-214 in the development and progression of BC. Our results revealed that miR-214 expression was significantly increased in the BC tissues compared with the adjacent benign tissues, and that the upregulation of miR-214 was significantly associated with the invasion ability of the BC cells. Furthermore, p53, which has been reported to be downregulated in BC, was predicted to be the target gene of miR-214 using bioinformatics software programs. Moreover, luciferase reporter vectors were constructed and it was confirmed that p53 is a target of miR-214. Following the transfection of miR-214 into BC cells, we found that the overexpression of miR-214 markedly enhanced cell invasion through the downregulation of p53 expression. By contrast, the overexpression of p53 abrogated the effects of miR-214. In conclusion, this study demonstrates that miR-214 functions as an oncogene in BC, at least partly by promoting cell invasion through the downregulation of p53. Therefore, miR-214 may be a potential therapeutic target for the treatment of BC.

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Section: Discussionmentioning

confidence: 98%

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

Wang

et al. 2015

International Journal of Molecular Medicine

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“…miR-214 participates in the control of cancer cell signaling networks and exhibits controversy functions via regulating several target genes. In fact, miR-214 behaves as a key hub not only by coordinating fundamental signaling networks such as PTEN/AKT, β-catenin, and tyrosine kinase receptor pathways, but also by regulating the levels of crucial gene expression modulators: the epigenetic repressor Ezh2, tumor suppressor p53, transcription factors TFAP2, and another microRNA, miR-148b [17,27,[30][31][32][33][34][35]. Thus, miR-214 seems to have essential roles in coordinating tumor proliferation, stemness, angiogenesis, invasiveness, extravasation, metastasis, and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

Zhang

2017

Bioscience Reports

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Correspondence: Shuxiang Zhang (zhang sx19@163.com) Ovarian cancer is one of the leading causes of death among gynecological malignancies. Increasing evidence indicate that dysregulation of microRNAs (miRNAs) plays an important role in tumor radioresistance. The aim of the present study is to investigate whether microRNA-214 (miR-214) was involved in radioresistance of human ovarian cancer. Here, we showed that miR-214 was significantly up-regulated in ovarian cancer tissues and radioresistance ovarian cancer cell lines. Transfection of miR-214 agomir in radiosensitive ovarian cancer cell lines promoted them for resistance to ionizing radiation, whereas transfection of miR-214 antagomir in radioresistance ovarian cancer cell lines sensitized them to ionizing radiation again. Furthermore, we found miR-214 effectively promoted tumor radioresistance in xenograft animal experiment. Western blotting and quantitative real-time PCR demonstrated that miR-214 negatively regulated PTEN in radioresistance ovarian cancer cell lines and ovarian cancer tissues. Taken together, our data conclude that miR-214 contributes to radioresistance of ovarian cancer by directly targeting PTEN.

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“…MiR-214 knockdown has been reported in some malignancies, including primary CNS lymphomas (PCNSL) [123]. In a study by MisiewiczKrzeminska et al, it was shown that miR-214 has tumor suppressor activity with positive regulation of p53 and inhibition of DNA replication in multiple myeloma patients, and re-expression of it in myeloma cells induces apoptosis and inhibits proliferation [124].…”

Section: Impact Of Twist On Mirnas Expressionmentioning

confidence: 98%

Twist as a new prognostic marker in hematological malignancies

et al. 2015

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Twist proteins are members of basic helix-loop-helix family and are major regulators of embryogenesis. In adult humans, Twist proteins are mainly expressed in precursor cells, including myogenic, osteoblastic, chondroblastic and myelomonocytic lineages, maintaining their undifferentiated state. In addition, they play important roles in lymphocyte function and maturation. Recently, several studies have reported regulatory roles for Twist in the function and development of hematopoietic cells as well as in survival and development of numerous hematological malignancies. It is activated by numerous signal transduction pathways, including Akt, nuclear factor κB, Wnt, signal transducer and activator of transcription 3, mitogen-activated protein kinase and Ras signaling. Activated Twist has an anti-apoptotic role and protects cancer cells from apoptotic cell death. In addition, overexpression of Twist promotes the process of epithelial-mesenchymal transition, which has an essential role in cancer metastasis. Hereby, we review the aberrant expression of Twist in hematopoietic malignancies such as leukemias, lymphomas and myelodysplastic syndrome, which is related with poor prognosis and drug resistance in these disorders. Inactivation of Twist by small RNAs technology or chemotherapeutic inhibitors targeting Twist and upstream or downstream molecules of Twist signaling pathways may be helpful in management of disease to improve treatment strategies in malignancies.

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Restoration of microRNA-214 expression reduces growth of myeloma cells through positive regulation of P53 and inhibition of DNA replication

Cited by 71 publications

References 45 publications

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

microRNA-214 enhances the invasion ability of breast cancer cells by targeting p53

miR-214 promotes radioresistance in human ovarian cancer cells by targeting PETN

Twist as a new prognostic marker in hematological malignancies

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