<p>microRNA-548b suppresses aggressive phenotypes of hepatocellular carcinoma by directly targeting high-mobility group box 1 mRNA</p>

Abstract

Background and purpose: An increasing number of studies have revealed that microRNAs (miRNAs) are the main drivers of hepatocarcinogenesis including progression to later stages of liver cancer. Recently, miR-548b was identified as a cancer-related miRNA in glioma and tongue squamous cell carcinoma. Nonetheless, the expression pattern and specific roles of miR-548b in hepatocellular carcinoma (HCC) have not yet been clarified. Methods: Expression levels of miR-548b in HCC tissues and cell lines were measured by reverse-transcription quantitative PCR. In vitro and in vivo functional assays were performed to determine the effects of miR-548b on the malignant phenotypes of HCC cells. In addition, the molecular mechanisms by which miR-548b regulates the initiation and progression of HCC were investigated in detail. Results: miR-548b expression was weak in HCC tissues and cell lines. The low miR-548b expression significantly correlated with tumor size, TNM stage, and venous infiltration of HCC. In addition, exogenous miR-548b expression suppressed HCC cell proliferation, colony formation, and metastasis and induced apoptosis in vitro. Silencing of miR-548b exerted an opposite effect on these characteristics of HCC cells. Furthermore, miR-548b overexpression hindered tumor growth in vivo. Mechanistic analysis identified high-mobility group box 1 (HMGB1) as a direct target gene of miR-548b in HCC cells. Moreover, an HMGB1 knockdown reproduced the effects of miR-548b upregulation on HCC cells. Recovered HMGB1 expression reversed the effects of miR-548b on HCC cells. Notably, miR-548b overexpression deactivated the PI3K-AKT pathway in HCC cells in vitro and in vivo. Conclusion: Our findings provide the first evidence that miR-548b restrains HCC progression, at least partially, by downregulating HMGB1 and deactivating the PI3K-AKT pathway. Thus, miR-548b might be a novel target for the development of new therapies for HCC.

miR-548b Suppresses Melanoma Cell Growth, Migration, and Invasion by Negatively Regulating Its Target Gene HMGB1

“…25 In HCC, miRNA-548b inhibits the invasive phenotypes of HCC cells by interacting with HGMB1. 24 All results point out that miR-548b plays an important role in cancer progression. However, the expression level and potential function of miR-548b in melanoma remain unclear.…”

“…26,48 Yun et al have demonstrated that miRNA-548b reduces the invasive behaviors of HCC by modulating HMGB1. 24 Lin et al performed an in vitro experiment of HCC cells and provided evidence that HCC cell growth and apoptosis are regulated by miR-548b. 48 Meanwhile, miR- 198 FENG 548-3p is markedly downregulated in breast cancer and overexpression of miR-548-3p inhibits proliferation and promotes the apoptosis of breast cancer cells.…”

“…23 Recently, miRNA-548b has been found to inhibit the aggressiveness of hepatocellular carcinoma (HCC) by regulating the high mobility group protein 1 (HMGB1). 24 In addition, miR-548b restrains the growth and aggressiveness of glioma by targeting metastasis tumor-associated protein-2 (MTAP2). 25 miR-548b is also expressed at a low level in HCC tissues and might serve as a tumor-suppressive miRNA in proliferation and invasion of HCC cells.…”

miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma

“…The miR-548b inhibits cells proliferation and enhances apoptosis in breast cancer [38]. The miR-548b also inhibits proliferation and invasion in malignant glioma [39] and hepatocellular carcinoma (HCC) [40,41]. On the other hand, in esophageal squamous cell carcinoma (ESCC), the miR-548 enhances cell migration and invasion [42].…”

Mechanism of miR‑98 inhibiting tumor proliferation and invasion by targeting IGF1R in diabetic patients combined with colon cancer

“…miRNAs do not encode any protein, but can regulate biological processes by inhibiting the expression level of target gene mRNA, thereby regulating the occurrence and progression of the disease (11)(12)(13). Studies have shown that miRNAs are differentially expressed in a variety of cancers, and differentially expressed miRNAs can be involved in the development and progression of cancer (14)(15)(16)(17), including colon cancer (18)(19)(20). For example, the expression level of miR-3653 is significantly downregulated in colon cancer tissues and cells, and the increased expression level of miR-3653 can significantly inhibit the migration and invasion of colon cancer cells by inhibiting the expression level of target gene Zeb2.…”