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MicroRNA-361-Mediated Inhibition of HSP90 Expression and EMT in Cervical Cancer Is Counteracted by Oncogenic lncRNA NEAT1.


ABSTRACT: Epithelial-mesenchymal transition (EMT) is a key process contributing to cervical cancer (CC) metastasis, and microRNAs (miRNAs) modulate the expression of genes implicated in EMT. However, the accurate role of miR-361 in CC-associated EMT and the mechanisms underlying its function in CC remains largely unknown. The functional roles of miR-361 in CC cells were explored by a series of cell functional assays. Luciferase reporter assays were used to demonstrate the potential interaction between miR-361, HSP90, and long non-coding RNA (lncRNA) NEAT1. We detected a reduction of miR-361 expression in CC tissues compared with normal tissues, and miR-361 overexpression inhibited invasion and EMT phenotypes of CC cells by directly targeting a key EMT activator HSP90. Additionally, we detected significantly higher levels of HSP90 in CC tissues compared with normal tissues, and high expression of HSP90 predicted a poorer prognosis. We further identified NEAT1 as a significantly upregulated lncRNA in CC tissues and high expression of NEAT1 was associated with worse survival in CC patients. NEAT1 directly repressed miR-361 expression and played an oncogenic role in CC cell invasion and sphere formation. Conclusions: These results demonstrated that miR-361 directly targets HSP90 to inhibit the invasion and EMT features, and NEAT1 functions as an oncogenic lncRNA that suppresses miR-361 expression and induces EMT and sphere formation in CC cells, thus providing critical insights into the molecular pathways operating in this malignancy.

SUBMITTER: Xu D 

PROVIDER: S-EPMC7140536 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-361-Mediated Inhibition of HSP90 Expression and EMT in Cervical Cancer Is Counteracted by Oncogenic lncRNA NEAT1.

Xu Daozhi D   Dong Peixin P   Xiong Ying Y   Yue Junming J   Konno Yosuke Y   Ihira Kei K   Kobayashi Noriko N   Todo Yukiharu Y   Watari Hidemichi H  

Cells 20200305 3


Epithelial-mesenchymal transition (EMT) is a key process contributing to cervical cancer (CC) metastasis, and microRNAs (miRNAs) modulate the expression of genes implicated in EMT. However, the accurate role of miR-361 in CC-associated EMT and the mechanisms underlying its function in CC remains largely unknown. The functional roles of miR-361 in CC cells were explored by a series of cell functional assays. Luciferase reporter assays were used to demonstrate the potential interaction between miR  ...[more]

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