Accumulating evidences indicate that microRNAs play a vital role in regulating tumor progression. However, the roles of miR-148b in hepatocellular carcinoma (HCC) are still largely unknown. In this study, our data showed that miR-148b was significantly downregulated in 40 pairs of human HCC tissues. Further, the deregulated miR-148b was significantly correlated with larger tumor size, more tumor number, metastasis and worse prognosis in HCC. Overexpression of miR-148b inhibited HCC HepG2 cells proliferation and tumorigenicity. Further, miR-148b induced cells apoptosis by activating caspase- 3 and caspase-9, and induced S phase arrest by regulating cyclinD1 and p21, and also inhibited cell invasion. Data from the dual-luciferase reporter gene assay showed that WNT1 was a direct target of miR-148b, and overexpressed WNT1 inversely correlated with miR-148b levels in HCC tissues. Silencing of WNT1 inhibited the growth of HCC cells, and also induced cells apoptosis and inhibited invasion, which is consistent with the effects of miR-148b overexpression. MiR-148b downregulated expression of WNT1, β-catenin and C-myc, while upregulated E-cadherin expression. We conclude that the frequently downregulated miR-148b can regulate WNT1/β-catenin signalling pathway and function as a tumor suppressor in HCC. These findings suggest that miR-148b may serve as a novel therapeutic target for HCC.
BackgroundThe objective of the study was to explore the clinical expression, radiological and pathological features, differential diagnosis, and biological behavior of a clear cell myomelanocytic tumor. In a case involving a clear cell myomelanocytic tumor located in the hepatic falciform ligament, we evaluated clinical expression, radiological characteristics, histopathology, immunohistochemistry, and biological behavior; we also reviewed the relevant literature.Case presentationClear cell myomelanocytic tumor is a benign soft-tissue neoplasm that often occurs in women, and is expressed as a painless mass. The falciform ligament is its most frequent site of occurrence. The imaging characteristics of this lesion were uneven enhancement in the arterial phase, continuing to strengthen in the venous phase, and equal density in the balance phase. Histological and immunohistochemical analysis revealed the main transparent epithelioid cells and smooth muscle spindle cells to be HMB-45(+), smooth muscle actin(+), and melan-A (+).ConclusionHepatic vascular epithelioid cell tumors are very rare mesenchymal neoplasms. Few studies have investigated this tumor in the hepatic falciform ligament; consequently, its diagnosis and the selection of an appropriate treatment and follow-up protocol are challenging. Treatment outcome remains unpredictable. Therefore, clear cell myomelanocytic tumor should be viewed as a tumor with uncertain malignant potential requiring long-term follow-up.
Abstract. microRNAs (miRNAs) have been proven to play key regulatory roles in hepatocarcinogenesis. In the present study, the possible role of microRNA-450a (miR-450a) in hepatocarcinogenesis was investigated. Our study revealed that miR-450a was significantly down-regulated in hepatocellular carcinoma (HCC) tissues compared with that in normal liver (NL) and para-tumorous (PT) tissues, and miR-450a expression in HepG2 cells was significantly lower than that in L02 cells. Both the mRNA and protein levels of the miR-450a potential target gene, DNA methyltransferase 3a (DNMT3a), were obviously higher in HCC compared with levels in the NL and PT tissues. We further identified DNMT3a as the direct target gene for miR-450a, and ectopic miR-450a expression in HepG2 cells caused the down-regulation of DNMT3a and an inhibition of cell proliferation. Taken together, these findings suggest that miR-450a plays an important regulatory role in hepatocarcinogenesis through inhibition of DNMT3a expression, and miR-450a may be a potential target for the treatment of HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, especially in East Asia, including China. However, the pathogenesis of hepatocarcinogenesis is far from clear. microRNAs (miRNAs) are a type of highly conserved non-coding small RNAs which regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, and apoptotic and viral infection. Recently, miRNAs have been found to play pivotal roles in many malignancies including HCC development (1-9). The presence of a molecular prognostic miRNA signature in primary HCC clinical specimens has also been confirmed by several recent studies (4,6,7,(10)(11)(12), and many miRNAs have been found to play important regulatory roles in hepatocarcinogenesis.Our previous study found that miRNA-602 has an important regulatory activity in HBV-mediated hepatocarcinogenesis by inhibiting the tumor-suppressive gene RASSF1A from very early stages of chronic HBV hepatitis to HBV-positive cirrhosis to HCC (13). In this study, the expression of miRNA-450a and its potential target, DNA methyltransferase 3a (DNMT3a), was investigated in HCC. Materials and methodsPatients and cell lines. Histologically normal liver samples were obtained by biopsy during surgery from eight patients with gallbladder stones. Thirty-four HCC and corresponding non-malignant para-tumorous specimens were collected by radical hepatectomy. All tissues were obtained with informed consent from the patients, and were verified by biochemistry and pathological examination. The study was approved by the Institutional Review Board of Tongji Medical College, Huazhong University of Science and Technology (China). The cell lines, HepG2 and L02, were cultured in RMPI-1640 with 10% fetal bovine serum.microRNA arrays. miR-450a from 8 normal livers, 34 HCC, and corresponding non-tumor...
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