Dataset Information

MiR-342-5p inhibits osteosarcoma cell growth, migration, invasion, and sensitivity to Doxorubicin through targeting Wnt7b.

ABSTRACT: Osteosarcoma (OS) accounts for 9 percent of cancer-related deaths in young people. The PI3K/Akt signaling, a well-known carcinogenic signaling pathway in human cancer, cooperates with other signaling pathways such as Wnt signaling to promote cancer progression. Wnt7b, as a transforming member of the Wnt family, could activate mTORC1 through PI3K-AKT signaling and is upregulated in OS. In the present study, we found that miR-342-5p inhibits Wnt7b expression via direct binding to Wnt7b 3'-UTR. miR-342-5p overexpression remarkably suppressed the viability and invasion while enhanced the apoptosis of OS cells; meanwhile, Wnt7b, ?-catenin, c-myc, and cyclin D1 proteins were reduced while E-cadherin protein showed to be increased. Consistent with its expression pattern, Wnt7b exerted oncogenic effects on OS cells. Wnt7b could significantly attenuate the impacts of miR-342-5p. In conclusion, we demonstrated a miR-342-5p/Wnt7b axis that regulates the capacity of OS cells to proliferate and to invade through Wnt/?-catenin signaling. The miR-342-5p/Wnt7b axis might be novel targets for OS targeted therapy, which needs further in vivo and clinical investigations.

SUBMITTER: Liu Q

PROVIDER: S-EPMC6927707 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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miR-342-5p inhibits osteosarcoma cell growth, migration, invasion, and sensitivity to Doxorubicin through targeting Wnt7b.

Liu Qing Q Wang Zhenting Z Zhou Xiaohua X Tang Mingying M Tan Wei W Sun Tianshi T Deng Youwen Y

Cell cycle (Georgetown, Tex.) 20191010 23

Osteosarcoma (OS) accounts for 9 percent of cancer-related deaths in young people. The PI3K/Akt signaling, a well-known carcinogenic signaling pathway in human cancer, cooperates with other signaling pathways such as Wnt signaling to promote cancer progression. Wnt7b, as a transforming member of the Wnt family, could activate mTORC1 through PI3K-AKT signaling and is upregulated in OS. In the present study, we found that miR-342-5p inhibits Wnt7b expression via direct binding to Wnt7b 3'-UTR. miR ...[more]

PMID: 31601147

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Project description:BackgroundStudies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174.MethodsHigh-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1).ResultsCompared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value < 0.05). Knockdown of circ_0001174 inhibited the proliferation, migration, and invasion of OS cells. Additionally, circ_0001174 directly and negatively modulated the expression of miR-186-5p and positively regulated the expression of MACC1.ConclusionsAbnormally high expression of circ_0001174 may promote the proliferation, migration, and invasion of OS cells through up-regulating MACC1 by sponging miR-186-5p. These results provide insight into therapeutic targets for preventing and treating OS.

Dataset Information

MiR-342-5p inhibits osteosarcoma cell growth, migration, invasion, and sensitivity to Doxorubicin through targeting Wnt7b.

Publications

miR-342-5p inhibits osteosarcoma cell growth, migration, invasion, and sensitivity to Doxorubicin through targeting Wnt7b.

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