miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

Bhattacharjya, Sumana; Nath, Somsubhra; Ghose, Jayeeta; Maiti, Guru Prasad; Biswas, Nupur; Bandyopadhyay, Santu; Panda, CK; Bhattacharyya, NP; Roychoudhury, Susanta

doi:10.1038/cdd.2012.135

Cited by 30 publications

(29 citation statements)

References 38 publications

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“…However, in human cancers, mutations in SAC genes are infrequent (23). This observation led to the speculation that SAC deregulation by cancer genes and microRNA(s) may act to induce these defects (56,57). Indeed, it has been shown that the tumor suppressor protein p53 regulates the transcription of Cdc20 (30).…”

Section: Discussionmentioning

confidence: 99%

Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

Nath

Chowdhury

Dey

et al. 2015

Molecular and Cellular Biology

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The E2F family of transcription factors regulates genes involved in various aspects of the cell cycle. Beyond the well-documented role in G 1 /S transition, mitotic regulation by E2F has also been reported. Proper mitotic progression is monitored by the spindle assembly checkpoint (SAC). The SAC ensures bipolar separation of chromosomes and thus prevents aneuploidy. There are limited reports on the regulation of the SAC by E2F. Our previous work identified the SAC protein Cdc20 as a novel transcriptional regulator of the mitotic ubiquitin carrier protein UbcH10. However, none of the Cdc20 transcription complex proteins have any known DNA binding domain. Here we show that an E2F1-DP1 heterodimer is involved in recruitment of the Cdc20 transcription complex to the UBCH10 promoter and in transactivation of the gene. We further show that inactivation of Rb can facilitate this transactivation process. Moreover, this E2F1-mediated regulation of UbcH10 influences mitotic progression. Deregulation of this pathway results in premature anaphase, chromosomal abnormalities, and aneuploidy. We conclude that excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10, leading to chromosomal instability in cancer cells.

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Section: Discussionmentioning

confidence: 99%

Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

Nath

Chowdhury

Dey

et al. 2015

Molecular and Cellular Biology

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“…miR-155 is overexpressed in pancreatic cancer cells and interacts with TP53INP1 mRNA at its 3′UTR (Gironella et al, 2007), whereas miR-125b is overexpressed in type II endometrial carcinoma cells and contributes to the malignancy of type II endometrial carcinoma, possibly through down-regulation of TP53INP1 expression (Jiang et al, 2011). Regulation of TP53INP1 expression by miR-125b can be potentially important for more effective therapy, since various studies have established miR-125b as an oncogene or tumor suppressor gene in difference types of human tumors (Bousquet et al, 2010; Zhang et al, 2011; Bhattacharjya et al, 2013). …”

Section: Micro Rnas Reduce Tp53inp1 Mrna Expressionmentioning

confidence: 99%

Tumor Protein 53-Induced Nuclear Protein 1 Enhances p53 Function and Represses Tumorigenesis

Shahbazi¹,

Lock²,

Liu³

2013

Front. Genet.

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Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a stress-induced p53-target gene whose expression is modulated by transcription factors such as p53, p73, and E2F1. TP53INP1 gene encodes two isoforms of TP53INP1 proteins, TP53INP1α and TP53INP1β, both of which appear to be key elements in p53 function. In association with homeodomain-interacting protein kinase-2 (HIPK2), TP53INP1 phosphorylates p53 protein at Serine-46. This enhances p53 protein stability and its transcriptional activity, leading to transcriptional activation of p53-target genes such as p21 and PIG3, cell growth arrest and apoptosis upon DNA damage stress. The anti-proliferative and pro-apoptotic activities of TP53INP1 indicate that TP53INP1 has an important role in cellular homeostasis and DNA damage response. Deficiency in TP53INP1 expression results in increased tumorigenesis, whereas TP53INP1 expression is repressed during early stages of cancer by factors such as miR-155. This review aims to summarize the roles of TP53INP1 in blocking tumor progression through p53-dependant and p53-independent pathways, as well as the elements which repress TP53INP1 expression, hence highlighting its potential as a therapeutic target in cancer treatment.

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“…In the present study we quantified nine miRNAs (miR-15a, miR-21, miR-29b, miR-34c, miR-100, miR-125b, miR-133b, miR-137 and miR-199b) in 32 samples from HNSCC, and eight of their resection margins by qRT-PCR, in order to determine whether their levels are associated with clinical pathological features. These specific miRs were chosen because they participate in the regulation of pathways considered to be “hallmarks of cancers”, such as cell death, proliferation and migration/invasion [10], [11], [12], [13], [14]. We also assessed by immunohistochemistry in six selected HNSCC samples and their matched resection margins the SET (I2PP2A) protein, involved in the promotion of cancer cell proliferation [15], and PTEN protein, a classic tumor suppressor [16].…”

Section: Introductionmentioning

confidence: 99%

Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR-199b levels in head and neck squamous cell carcinoma

et al. 2016

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BackgroundMicroRNAs (miRNAs or miRs) are post-transcriptional regulators of eukaryotic cells and knowledge of differences in miR levels may provide new approaches to diagnosis and therapy.MethodsThe present study measured the levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and determined whether clinical pathological features are associated with differences in miR levels. SET (I2PP2A) and PTEN protein levels were also measured, since their levels can be regulated by miR-199b and miR-21, respectively. Nine miRs (miR-15a, miR-21, miR-29b, miR-34c, miR-100, miR-125b, miR-137, miR-133b and miR-199b) were measured by real time qRT-PCR in HNSCC samples from 32 patients and eight resection margins. SET (I2PP2A) and PTEN protein levels were estimated by immunohistochemistry in paired HNSCC tissues and their matched resection margins.ResultsIn HNSCC, the presence of lymph node invasion was associated with low miR-15a, miR-34c and miR-199b levels, whereas the presence of perineural invasion was associated with low miR-199b levels. In addition, miR-21 levels were high whereas miR-100 and miR-125b levels were low in HNSCC compared to the resection margins. When HNSCC line HN12, with or without knockdown of SET, were transfected with miR-34c inhibitor or miR-34c mimic, the miR-34c inhibitor increased cell invasion capacity while miR-34c mimic decreased the cell invasion.ConclusionsWe showed that the levels of specific miRs in tumor tissue can provide insight into the maintenance and progression of HNSCC.General significanceMiRNAs are up- or down-regulated during cancer development and progression; they can be prognosis markers and therapeutic targets in HNSCC.

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miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression

Cited by 30 publications

References 38 publications

Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

Tumor Protein 53-Induced Nuclear Protein 1 Enhances p53 Function and Represses Tumorigenesis

Lymph node or perineural invasion is associated with low miR-15a, miR-34c and miR-199b levels in head and neck squamous cell carcinoma

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