MicroRNA-542-3p inhibits the growth of hepatocellular carcinoma cells by targeting FZD7/Wnt signaling pathway.

MicroRNAs (miRNA) are relevant regulators of the tumorigenesis of various cancers, such as hepatocellular carcinoma (HCC). Recent studies have suggested that miR-542-3p is a tumor suppressor gene in numerous cancers. However, the role of miR-542-3p in HCC remains unclear. This study showed that miR-542-3p was downregulated in HCC tissues and cell lines. MTT, colony formation, and cell cycle assays revealed that miR-542-3p overexpression inhibited HCC cell growth, whereas miR-542-3p suppression promoted cell growth. Frizzled7 (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-542-3p through dual-luciferase reporter assay, RT-qPCR, and Western blot. The mRNA expression of FZD7 was inversely correlated with miR-542-3p expression in HCC tissues. miR-542-3p overexpression could significantly decrease the activation of Wnt signaling pathway in HCC cells. FZD7 overexpression could significantly reverse the inhibitory effect of miR-542-3p on HCC cell growth and Wnt signaling pathway. Taken together, our study suggests that miR-542-3p inhibits HCC cell growth by targeting FZD7 and inhibiting Wnt signaling pathway. The decreased miR-542-3p expression may also contribute to the progression of HCC and may represent a novel molecular therapeutic target for HCC.

Wu W ，Dang S ，Feng Q ，Liang J ，Wang Y ，Fan N ... -  《-》

MicroRNA-504 functions as a tumor suppressor in hepatocellular carcinoma through inhibiting Frizzled-7-mediated-Wnt/β-catenin signaling.

Accumulating evidence suggests that microRNAs (miRNAs) are critical regulators in the development and progression of various malignant tumors, including hepatocellular carcinoma (HCC). Multiple findings have indicated that miRNA-504 (miR-504) is dysregulated in several types of cancers, functioning as an oncogenic miRNA or a tumor suppressive miRNA. However, the role of miR-504 in HCC remains unknown. In this study, we aimed to detect the expression pattern of miR-504 in HCC tissues and cell lines and investigate the precise biological function in HCC cells. Our results showed that miR-504 expression levels were frequently downregulated in both HCC tissues and cell lines. Gain-of-function experiments demonstrated that miR-504 overexpression inhibited the proliferation and invasion in HCC cell lines. By contrast, miR-504 inhibition had the opposite effect. Interestingly, bioinformatics analysis predicted that Frizzled-7 (FZD7) was a potential target gene of miR-504. Dual-luciferase reporter assays confirmed that miR-504 directly targeted the 3'-untranslated region of FZD7 mRNA. In addition, our results showed that miR-504 negatively regulated the mRNA and protein expression of FZD7 in HCC cell lines. Moreover, miR-540 overexpression inhibited the cellular expression of β-catenin and blocked the activation of Wnt signaling in HCC cells. Notably, restoration of FZD7 expression significantly reversed the inhibitory effect of miR-504 on proliferation, invasion, and Wnt/β-catenin signaling in HCC cells. In conclusion, our results demonstrate that miR-504 functions as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by targeting FZD7 and inhibiting Wnt/β-catenin signaling. Our study provides evidence that miR-504-meidated FZD7/Wnt/β-catenin signaling pathway plays an important role in HCC development and progression and suggests miR-504 as a novel future therapeutic target for treatment of HCC.

Quan H ，Li B ，Yang J 《-》

MicroRNA-613 represses prostate cancer cell proliferation and invasion through targeting Frizzled7.

A growing number of studies have indicated that microRNAs (miRNAs) are critical regulators of carcinogenesis and cancer progression and may serve as potential therapeutic tools for cancer therapy. Frizzled7 (Fzd7), the most important receptor of the Wnt signaling pathway, is extensively involved in cancer development and progression. However, the role of Fzd7 in prostate cancer remains unclear. In this study, we aimed to explore the expression of Fzd7 in prostate cancer and test whether modulating Fzd7 expression by miR-613 would have an impact on prostate cancer cell proliferation and invasion. We found that Fzd7 was highly expressed in prostate cancer cell lines. Through bioinformatics analysis, Fzd7 was predicted as a target gene of miR-613, which was validated by dual-luciferase reporter assays, real-time quantitative polymerase chain reaction and Western blot analysis. By gain of function experiments, we showed that overexpression of miR-613 significantly suppressed prostate cancer cell proliferation and invasion. Furthermore, miR-613 overexpression markedly downregulated the Wnt signaling pathway. Through a rescue experiment, we showed that overexpression of Fzd7 could abrogate the inhibitory effect of miR-613 on cell proliferation and invasion as well as Wnt signaling. Additionally, these results were further strengthened by data showing that miR-613 was significantly downregulated in prostate cancer tissues, exhibiting an inverse correlation with Fzd7 expression. In conclusion, our study suggests that miR-613 functions as a tumor suppressor, partially through targeting Fzd7, and is a potential therapeutic target for prostate cancer.

Ren W ，Li C ，Duan W ，Du S ，Yang F ，Zhou J ，Xing J ... -  《-》

MicroRNA-485-5p represses melanoma cell invasion and proliferation by suppressing Frizzled7.

MicroRNAs (miRNAs) have emerged as critical regulators for malignant melanoma development. miR-485-5p has been suggested as a tumor-suppressive miRNA in many types of human malignancies. However, the role of miR-485-5p in melanoma remains unknown. In this study, we aimed to explore the potential role and underlying mechanism of miR-485-5p in the regulation of melanoma development. Here, we showed that miR-485-5p was significantly decreased in melanoma tissues and cell lines compared with their corresponding controls. Transwell invasion assay showed that miR-485-5p overexpression markedly inhibited melanoma cell invasion. WST-1 and cell cycle assays exhibited that miR-485-5p overexpression significantly suppressed melanoma cell proliferation. By contrast, miR-485-5p suppression promoted the invasion and proliferation of melanoma cells. Using bioinformatics analysis, we observed that miR-485-5p potentially targets the 3'-untranslated region (3'-UTR) of Frizzled7 (FZD7). Dual-luciferase assay confirmed the direct binding between miR-485-5p and FZD7 3'-UTR. Meanwhile, real-time quantitative polymerase chain reaction and Western blot analysis showed that miR-485-5p overexpression suppressed FZD7 expression, whereas miR-485-5p suppression resulted in the opposite effect. Moreover, miR-485-5p expression was observed to be inversely correlated with FZD7 mRNA expression in melanoma tissues. Further experiments showed that miR-485-5p regulated Wnt signaling. The restoration of FZD7 expression markedly reversed the antitumor effects induced by miR-485-5p overexpression in melanoma cells. Taken together, our study suggests that miR-485-5p represses melanoma cell invasion and proliferation by suppressing FZD7, indicating a new tumor-suppressive role for miR-485-5p in melanoma. The miR-485-5p/FZD7 axis may provide novel insights into understanding the molecular pathogenesis of melanoma and may be a promising therapeutic target for melanoma.

Wu J ，Li J ，Ren J ，Zhang D ... -  《-》

Long non-coding RNA DSCR8 acts as a molecular sponge for miR-485-5p to activate Wnt/β-catenin signal pathway in hepatocellular carcinoma.

Wang Y ，Sun L ，Wang L ，Liu Z ，Li Q ，Yao B ，Wang C ，Chen T ，Tu K ，Liu Q ... -  《Cell Death & Disease》