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Nc886 is induced by TGF-? and suppresses the microRNA pathway in ovarian cancer.

ABSTRACT: Transforming growth factor-? (TGF-?) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-? signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified non-coding RNA implicated in several malignancies. The high expression of nc886 is associated with poor prognosis in 285 OC patients. Herein, we find that in OC nc886 expression is induced by TGF-? and that nc886 binds to Dicer to inhibit miRNA maturation. By preventing the miRNA pathway, nc886 emulates TGF-? in gene expression patterns and potentiates cell adhesion, migration, invasion, and drug resistance. Here we report nc886 to be a molecular link between the TGF-? and miRNA pathways.

SUBMITTER: Ahn JH

PROVIDER: S-EPMC5862949 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer.

Ahn Ji-Hye JH Lee Hyun-Sung HS Lee Ju-Seog JS Lee Yeon-Su YS Park Jong-Lyul JL Kim Seon-Young SY Hwang Jung-Ah JA Kunkeaw Nawapol N Jung Sung Yun SY Kim Tae Jin TJ Lee Kwang-Soo KS Jeon Sung Ho SH Lee Inhan I Johnson Betty H BH Choi Jung-Hye JH Lee Yong Sun YS

Nature communications 20180321 1

Transforming growth factor-β (TGF-β) signaling and microRNAs (miRNAs) are important gene regulatory components in cancer. Usually in advanced malignant stages, TGF-β signaling is elevated but global miRNA expression is suppressed. Such a gene expression signature is well illustrated in a fibrosis (or mesenchymal) subtype of ovarian cancer (OC) that is of poor prognosis. However, the interplay between the two pathways in the OC subtype has not yet been elucidated. nc886 is a recently identified n ...[more]

PMID: 29563500

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Project description:Background: Ovarian cancer (OC) is the second most common gynecological malignancy and has a high mortality rate. The current chemotherapeutic drugs have the disadvantages of drug resistance and side effects. Myricetin, a kind of natural compound, has the advantages of easy extraction, low price, and fewer side effects. Multiple studies have demonstrated the anti-cancer properties of myricetin. However, its impact on OC is still unknown and needs further investigation. Therefore, this study aimed to elucidate the mechanism by which myricetin suppresses transforming growth factor-β (TGF-β) -induced epithelial-to-mesenchymal transition (EMT) in OC through in vivo and in vitro experiments. Methods: In vitro experiments were conducted to evaluate the effects of myricetin on cell proliferation and apoptosis using CCK8 assay, plate clonal formation assay, and flow cytometry. Western blot was employed to evaluate the expression levels of caspase-3, PARP, and the MAPK/ERK and PI3K/AKT signaling pathways. Wound healing, transwell, western blot and immunofluorescence assay were used to detect TGF-β-induced cell migration, invasion, EMT and the levels of Smad3, MAPK/ERK, PI3K/AKT signaling pathways. Additionally, a mouse xenograft model was established to verify the effects of myricetin on OC in vivo. Results: Myricetin inhibited OC proliferation through MAPK/ERK and PI3K/AKT signaling pathways. Flow cytometry and western blot analyses demonstrated that myricetin promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase-3 and the ratio of Bax/Bcl-2 in OC. Furthermore, myricetin suppressed the TGF-β-induced migration and invasion by transwell and wound healing assays. Mechanistically, western blot indicated that myricetin reversed TGF-β-induced metastasis through Smad3, MAPK/ERK and PI3K/AKT signaling pathway. In vivo, myricetin significantly repressed OC progression and liver and lung metastasis. Conclusion: Myricetin exhibited inhibitory effects on OC progression and metastasis both in vivo and in vitro. And it also reversed TGF-β-induced EMT through the classical and non-classical Smad signaling pathways.

Dataset Information

Nc886 is induced by TGF-? and suppresses the microRNA pathway in ovarian cancer.

Publications

nc886 is induced by TGF-β and suppresses the microRNA pathway in ovarian cancer.

Similar Datasets

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