Differential microRNA expression profiles between malignant rhabdoid tumor and epithelioid sarcoma: miR193a-5p is suggested to downregulate SMARCB1 mRNA expression

作者：Kohashi Kenichi; Yamamoto Hidetaka; Kumagai Reiko; Yamada Yuichi; Hotokebuchi Yuka; Taguchi Tomoaki; Iwamoto Yukihide; Oda Yoshinao^*

来源：Modern Pathology, 2014, 27(6): 832-839.

DOI：10.1038/modpathol.2013.213

• epithelioid sarcoma
• malignant rhabdoid tumor
• microRNA

Malignant rhabdoid tumor and epithelioid sarcoma are classified as tumors of uncertain differentiation. However, it is controversial whether these tumors are distinct entities because they share similar histological and immunohistochemical features such as the existence of rhabdoid cells or complete loss of SMARCB1 protein expression. MicroRNAs are small non-coding RNAs, and it is suggested that knowledge of microRNA expression profiles in cancer may have substantial value for diagnostics. We first analyzed microRNA expression profiles in 13 frozen materials (five malignant rhabdoid tumors, two proximal type epithelioid sarcomas, and six conventional type epithelioid sarcomas) and subsequently examined the specific microRNA expressions in 29 paraffin-embedded materials (8 malignant rhabdoid tumors, 13 proximal type epithelioid sarcomas, and 8 conventional type epithelioid sarcomas) and 13 previously described frozen materials by quantitative RT-PCR. According to the unsupervised hierarchical clustering of microRNA, proximal type epithelioid sarcoma and conventional type epithelioid sarcoma were classified into the same category, whereas malignant rhabdoid tumor was a distinct category from both types of epithelioid sarcoma. In addition, when malignant rhabdoid tumor with SMARCB1 gene alterations and proximal type and conventional type epithelioid sarcoma with no SMARCB1 gene alterations were compared, 56 microRNAs were isolated as being significantly different (ANOVA, P<0.05). Among them, quantitative RT PCR using frozen and paraffin-embedded materials demonstrated that expression levels of miR193a-5p (P=0.002), which has been suggested to downregulate SMARCB1 mRNA expression, showed statistically different expression levels between malignant rhabdoid tumor and epithelioid sarcoma with no SMARCB1 gene alterations. These results suggest that epithelioid sarcoma, especially proximal type epithelioid sarcoma, and malignant rhabdoid tumor are distinct tumors with respect to the microRNA expression profiles and that miR193a-5p may have an important role in the inhibition of SMARCB1 mRNA expression.

• 出版日期2014-6