HMGA2 mRNA Research Articles

Determination of High Mobility Group A1 (HMGA1) Expression in Hepatocellular Carcinoma: A Potential Prognostic Marker

Our objective was to investigate the expression of HMGA1 mRNA and protein in hepatocellular carcinoma (HCC) and the correlation between its expression and clinical pathological characteristics and prognosis. HMGA1 expression was determined at both the mRNA level and the protein level in 30 HCC tissues and their corresponding paracancer liver tissues (PCLTs) and 2 normal liver tissues by RT-PCR and IHC. Follow-up study was done on the 30 patients involved in this research. HMGA1 mRNA was detected in nine cases of HCC tissues and two PCLTs, for a positivity rate of 30% and 6.7%, respectively (P < 0.05), whereas no HMGA1 mRNA expression was found in normal liver tissues. Clinicopathological analysis revealed that HMGA1 mRNA expression was significantly correlated with Edmondson's grade (P < 0.05). HMGA1 protein was detected in four HCC tissues by IHC and located mainly in the nuclei; no positive staining was found in PCLTs. Follow-up study showed that HMGA1 mRNA-positive patients had a higher risk of recurrence/metastasis and a shorter survival than negative cases (P < 0.05). Our findings indicate that HMGA1 may be involved in the carcinogenesis and invasiveness of HCC and the determination of HMGA1 can be of great value in predicting the prognosis of patients with HCC.

HMGA2 is associated with invasiveness but not a suitable marker for the detection of circulating tumor cells in breast cancer

Previously, the human high mobility group protein member HMGA2 mRNA was reported to be expressed in peripheral blood of patients with breast cancer, but not in healthy individuals. Expression of HMGA2 in blood was suggested to be an independent indicator of poor prognosis in metastatic breast cancer. These very promising findings propose HMGA2 as a potential marker for the detection of circulating tumor cells in peripheral blood. Therefore, we analyzed peripheral blood specimens from healthy controls and patients with breast tumors for HMGA2 expression using TaqMan real-time RT-PCR to test if HMGA2 is a suitable marker for the early detection of breast cancer and monitoring therapy response in peripheral blood. Furthermore, we examined the possible involvement of HMGA2 expression in invasion investigated by an in vitro invasion assay using established breast cell lines. HMGA2 expression was detected in peripheral blood of breast cancer patients as well as of healthy individuals. No significant association of HMGA2 expression with any clinical or histopathological data was apparent. However, there was a significant correlation of HMGA2 expression in invasive and non invasive breast cell lines (p=0.0056). Although, HMGA2 obviously contributes to invasion it is not a specific marker for the detection of circulating tumor cells in peripheral blood.

HMGA2 locus rearrangement in a case of acute lymphoblastic leukemia

We report the first case of acute lymphoblastic leukemia associated with a t(9;12)(p22;q14) translocation within the HMGA2 locus. The breakpoint lies in the 5' region. Fluorescence in situ hybridization with a BAC clone covering the 5' region produced three signals versus two signals with a BAC clone covering the 3' region including intron 3 of HMGA2, which harbors most of the breakpoints described in benign mesenchymal tumors. HMGA2 locus rearrangement was associated with overexpression of an HMGA2 mRNA that lacked a carboxy-terminal tail. These results suggest that the HMGA2 gene rearrangement may contribute to the malignancy in leukemias harboring a 12q translocation.

Histone deacetylase inhibition is associated with transcriptional repression of the Hmga2 gene.

The high-mobility-group A2 protein (HMGA2) plays important functional roles in transcriptional regulation, DNA replication and chromatin structure. In this study, the effect of histone deacetylase inhibition on the transcriptional activity of the Hmga2 gene was investigated in vivo both at the endogenous gene level and in a variety of cell lines using transiently transfected promoter constructs. Trichostatin A (TSA) repressed both transfected murine and human Hmga2 promoter constructs 3-8-fold in NIH3T3, F9 and HeLa cells. Steady-state Hmga2 mRNA levels in NIH3T3 cells decreased 4-5-fold following TSA treatment, while pre- treatment of NIH3T3 cells with the transcriptional inhibitor, actinomycin D, completely blocked TSA mediated repression of the Hmga2 gene. Cross-linked chromatin immunoprecipitation (X-ChIP) analysis revealed a 5-6-fold decrease in endogenous Hmga2 promoter bound Sp1 and Sp3 proteins following TSA treatment in parallel with observed loss of acetylated histone H3 and H4. In addition, the poly-pyrimidine-tract-binding protein (PTB) was observed to bind to the Hmga2 promoter in both TSA treated and untreated NIH3T3 cells. Together, these results suggest TSA treatment leads to a decrease in Hmga2 gene transcription, and a significant decrease in promoter bound Sp1, Sp3 and acetylated histones H3 and H4.