HMGA molecular network: From transcriptional regulation to chromatin remodeling

Sgarra, Riccardo; Zammitti, Salvina; Sardo, Alessandra Lo; Maurizio, E; Arnoldo, Laura; Pegoraro, Silvia; Giancotti, Vincenzo; Manfioletti, Guidalberto

doi:10.1016/j.bbagrm.2009.08.009

Cited by 101 publications

(107 citation statements)

References 68 publications

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“…It is reported that HMGA2 binds the complex formed by pRB and HDAC1 to dissociate pRB from genomic promoter regions and promotes the transcriptional activity of E2F1 and blocks the G1/S transition to inhibit the cell proliferation (22). It has been discovered that HMGA2 is upregulated in many benign and malignant tumors, such as colorectal, breast, pancreatic, ovarian, and lung cancer (25)(26)(27)(28). In the present study, it was found that the mRNA and protein levels of HMGA2 were often upregulated in GBC tissues.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2

Zhou

Guo

Zhao

et al. 2014

International Journal of Oncology

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Abstract. MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNA molecules which can act as oncogenes or tumor suppressor genes in human cancer. However, the possible functions and mechanisms of miRNA action in gallbladder cancer (GBC) have not been elucidated. In the present study, it was found that miR-26a was often downregulated in GBC and the expression of miR-26a was associated with neoplasm histological grade. miR-26a significantly inhibited the proliferation of GBC cells based on the gain-of-function assays. Furthermore, we demonstrated that high mobility group AT-hook 2 (HMGA2) was a direct target of miR-26a. The results showed that HMGA2 mRNA levels and miR-26a levels were negatively correlated. In addition, we confirmed that reintroduction of HMGA2 antagonized the inhibition of miR-26a to GBC cell proliferation and all these effects were achieved through the cell cycle. Together, all these results suggest that miR-26a expression contributes to GBC proliferation by targeting HMGA2. miR-26a shows promise as a prognosis factor and therapeutic target of GBC patients. IntroductionMicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNAs which act as post-trancriptional regulators via binding to the 3' untranslated regions (3'-UTRs) of the target gene mRNA, and have vital functions in many of physiological and pathological processes, as well as in carcinogenesis (1-5). It has been reported that miRNAs can act as oncogene or tumor suppressor gene in various cancers, including lung, colorectal, and liver cancer (6,7).Gallbladder cancer (GBC) with poor prognosis is one of the most prevalent and aggressive malignant types of cancer in China. GBC is the tenth most common cancer in Shanghai and the average survival of patients is ~9 months (8). Many patients have no chance to accept radical operation when they are diagnosed. Despite its poor prognosis and high morbidity, the miRNA function in GBC remains largely unknown.The miRNA microarray assays performed on 4 pairs of GBC and paracancerous tissues, revealed that miR-26a is significantly downregulated in GBC tissues. It has been reported that miR-26a was downregulated in pancreatic, nasopharyngeal, breast and lung cancer, and miR-26a can acts as tumor suppressor gene via directly targeting enhancer of Zeste homolog 2 (EZH2) (9-12). Also in hepatocellular carcinoma cells, miR-26a can inhibit cell proliferation by regulating cyclin D2,14). It has been demonstrated that expression levels of miR-26a are lower in the tumors of renal cell carcinoma patients who developed tumor relapse, moreover, the lowest levels of miR-26a are observed in primary metastatic tumors (15). These findings suggested that miR-26a might play a vital role in GBC physiological and pathological processes.In the present study, we demonstrated that miR-26a is significantly downregulated in GBC tissues compared with paracancerous tissues and miR-26a is closely correlated with the histologic grade of the neoplasm. Enforced, highly expressed miR-26a was able to inhibit G...

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Section: Discussionmentioning

confidence: 99%

MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2

Zhou

Guo

Zhao

et al. 2014

International Journal of Oncology

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“…BA (analogously to methoxy amine) reacts with the baseless deoxyribose moieties (in intact or cleaved AP sites) rendering them refractory to mammalian AP endonuclease 1 and AP/dRP lyase activities . Direct interaction of HMGA2 with APE1 in vitro and in vivo (Sgarra et al, 2008, Summer et al, 2009, Sgarra et al, 2010 has been reported. However, the influence of HMGA2 on the AP endonuclease 1 activity is still unknown.…”

Section: Hmga As Cofactor Of the Ber Processmentioning

confidence: 99%

New Players in Recognition of Intact and Cleaved AP Sites: Implication in DNA Repair in Mammalian Cells

Ходырева¹,

Lavrik²

2011

Selected Topics in DNA Repair

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“…Its biological functions are not well understood, but its structural similarity to the high mobility group A (HMGA) proteins suggests that it may play a role in regulation of chromatin structure and its activity [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors

Zduniak¹,

Agrawal²,

Symonowicz³

et al. 2014

pjp

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Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NU-CKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential.

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HMGA molecular network: From transcriptional regulation to chromatin remodeling

Cited by 101 publications

References 68 publications

MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2

MicroRNA-26a acts as a tumor suppressor inhibiting gallbladder cancer cell proliferation by directly targeting HMGA2

New Players in Recognition of Intact and Cleaved AP Sites: Implication in DNA Repair in Mammalian Cells

The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors

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