MicroRNAs 221 and 222 Bypass Quiescence and Compromise Cell Survival

Medina, Ricardo; Zaidi, Sayyed K.; Liu, Chang–Gong; Stein, Janet L.; vanWijnen, André J.; Croce, Carlo M.; Stein, Gary S.

doi:10.1158/0008-5472.can-07-6754

Cited by 283 publications

(285 citation statements)

References 43 publications

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“…49,50 We note that in different cell lines mir-222 can induce either an S-phase or G1-accumulation. 51,52 This highlights that the effect of mir-222, similar to mir-155 and perhaps most microRNAs, is context specific.…”

Section: Regulation Of the Mir-424-503 Polycistronmentioning

confidence: 89%

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Forrest

Kanamori-Katayama²,

Tomaru³

et al. 2009

Leukemia

233

170

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Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced microRNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.

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Section: Regulation Of the Mir-424-503 Polycistronmentioning

confidence: 89%

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Forrest

Kanamori-Katayama²,

Tomaru³

et al. 2009

Leukemia

233

170

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“…Recently, 2 miRs (miR-221 and miR-222) were reported to downregulate the expression of both p27 Kip1 and p57 Kip2 transcripts (23)(24)(25)(26)(27)(28). Intriguingly, miR-221 and miR-222 also control the transcripts of several other important genes, including Kit, Gax/Meox2, Pten, Timp3, Bmf, Mdm2, Stat, and Puma.…”

Section: Structure and Regulation Of The Cdkn1c Genementioning

confidence: 99%

“…In some instances, their upregulation has been associated with a decrease of p57 Kip2 in malignant cell lines and cancer specimens, including gastric, ovarian, colorectal, and hepatic carcinomas (23)(24)(25). However, miR-221 and miR-222 control a number of pivotal transcripts, including p27 Kip1 .…”

Section: Mechanisms Of P57 Kip2 Decrease In Human Tumorsmentioning

confidence: 99%

p57Kip2 and Cancer: Time for a Critical Appraisal

Borriello

Caldarelli

Bencivenga

et al. 2011

Molecular Cancer Research

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p57Kip2 is a cyclin-dependent kinase inhibitor belonging to the Cip/Kip family, which also includes p21Cip1 and p27Kip1. So far, p57Kip2 is the least-studied Cip/Kip protein, and for a long time its relevance has been related mainly to its unique role in embryogenesis. Moreover, genetic and molecular studies on animal models and patients with Beckwith-Wiedemann syndrome have shown that alterations in CDKN1C (the p57Kip2 encoding gene) have functional relevance in the pathogenesis of this disease. Recently, a number of investigations have identified and characterized heretofore unexpected roles for p57Kip2. The protein appears to be critically involved in initial steps of cell and tissue differentiation, and particularly in neuronal development and erythropoiesis. Intriguingly, p27Kip1, the Cip/Kip member that is most homologous to p57Kip2, is primarily involved in the process of cell cycle exit. p57Kip2 also plays a critical role in controlling cytoskeletal organization and cell migration through its interaction with LIMK-1. Furthermore, p57Kip2 appears to modulate genome expression. Finally, accumulating evidence indicates that p57Kip2 protein is frequently downregulated in different types of human epithelial and nonepithelial cancers as a consequence of genetic and epigenetic events. In summary, the emerging picture is that several aspects of p57Kip2's functions are only poorly clarified. This review represents an appraisal of the data available on the p57Kip2 gene and protein structure, and its role in human physiology and pathology. We particularly focus our attention on p57Kip2 changes in cancers and pharmacological approaches for modulating p57Kip2 levels. Mol Cancer Res; 9(10); 1269–84. ©2011 AACR.

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“…For example, miR-21, one of the best characterized cancer-associated miRNAs, is highly expressed in GBM and has multi-faced functions such as inhibition of apoptosis and growth promotion [17,18]. miR-221 and miR-222 are other up-regulated miRNAs in GBM [19][20][21].…”

Section: Introductionmentioning

confidence: 99%

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

Ujifuku¹,

Mitsutake²,

Takakura³

et al. 2010

Cancer Letters

211

137

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Running title: miRNAs and temozolomide resistance in glioblastoma Key words: glioblastoma, resistance, microRNA,, miR-10a*, temozolomide. ABSTRACTTo identify microRNAs (miRNAs) specifically involved in the acquisition of temozolomide (TMZ) resistance in glioblastoma multiforme (GBM), we first established a resistant variant, U251R cells from TMZ-sensitive GBM cell line, U251MG. We then performed a comprehensive analysis of miRNA expressions in U251R and parental cells using miRNA microarrays. miR-195, miR-455-3p and miR-10a* were the three most up-regulated miRNAs in the resistant cells. To investigate the functional role of these miRNAs in TMZ resistance, U251R cells were transfected with miRNA inhibitors consisting of DNA/LNA hybrid oligonucleotides. Suppression of miR-455-3p or miR-10a* had no effect on cell growth, but showed modest cell killing effect in the presence of TMZ. On the other hand, knockdown of miR-195 alone displayed moderate cell killing effect, and combination with TMZ strongly enhanced the effect. In addition, using in silico analysis combined with cDNA microarray experiment, we present possible mRNA targets of these miRNAs. In conclusion, our findings suggest that those miRNAs may play a role in acquired TMZ resistance and could be a novel target for recurrent GBM treatment.

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MicroRNAs 221 and 222 Bypass Quiescence and Compromise Cell Survival

Cited by 283 publications

References 43 publications

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

p57Kip2 and Cancer: Time for a Critical Appraisal

miR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells

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