HMGA2: A biomarker significantly overexpressed in high-grade ovarian serous carcinoma

Abstract

Ovarian carcinoma consists of a group of histologically heterogeneous diseases involving distinct tumorigenic pathways. High-grade papillary serous carcinoma of the ovary is commonly associated with p53 mutations. HMGA2, an oncofetal protein, is found to be overexpressed in ovarian cancer. To study the function of HMGA2 in ovarian cancer, it is important to know which subtypes of ovarian cancer are associated with HMGA2 overexpression. In this study, we collected six different types of ovarian cancer and examined HMGA2 expression by immunohistochemistry, along with HMGA1, p53 and Ki-67. We found that HMGA2 overexpression was significantly higher in high-grade papillary serous carcinoma (64%) and carcinosarcoma (60%) than in other types of ovarian cancers (7-23%). HMGA2 overexpression was moderately associated with dominant p53 mutations (R ¼ 0.51). In addition, the microRNA in situ analysis revealed that let-7b, the HMGA2-negative regulators, were significantly lost in high-grade serous carcinoma. Our findings suggest that HMGA2 is an important molecular change significantly related to high-grade papillary serous carcinoma and is less common in other histological types of ovarian cancer.

Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma

“…11,25 We propose that MIR182 overexpression in high-grade serous ovarian carcinoma may be in part or completely responsible for HMGA2 overexpression. Although MIR182 and HMGA2 overexpression are found in nearly 70% of high-grade serous ovarian carcinoma (this study and Mahajan et al 16 and Wei et al 17 ), low correlation of expression of these two genes was found (r ¼ 0.23) in this study. This could be due to the fact that HMGA2 can be regulated by many microRNAs, such as the wellcharacterized ones in the let-7 family.…”

“…This could be due to the fact that HMGA2 can be regulated by many microRNAs, such as the wellcharacterized ones in the let-7 family. 26,27 Nevertheless, we found HMGA2 overexpression is significantly associated with high-grade serous ovarian carcinoma 16 in this study (Table 4).…”

“…16,17 The major tumorigenic functions of HMGA2 in the pathogenesis of high-grade serous ovarian carcinoma likely include regulation of epithelial mesenchymal transition. 24 A study by Ahmed et al 25 shows that BRCA1, ZBRK1 and CtIP form a repression complex that coordinately inhibits HMGA2 expression via a ZBRK1 recognition site in the HMGA2 promoter.…”

“…The latter finding was consistent with our previous study. 16 MIR182 overexpression and FOXO3a downregulation were significantly associated with advanced stage IV carcinoma (Po0.02 and 0.07, respectively). No significant asso- (Table 3).…”

HMGA2 Gene Silencing Suppression SW480 Colon Cancer Cell Invasion and Expression of Survivin

“…MDM2 transcription level was inhibited when the P53 activation ,this block the apoptosis of tumor cells [6,7]; But whether HMGA2 can be combined with P53, no studies have reported. However, studies have found, HMGA2 in invasive ovarian cancer tissue was significantly correlated with the expression level of P53, the progress of the process involved in ovarian cancer [8], it suggesting that HMGA2 may affect P53 expression .…”