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Long non-coding RNA EWSAT1 promoted metastasis and actin cytoskeleton changes via miR-24-3p sponging in osteosarcoma.


ABSTRACT: Non-coding RNAs are closely associated with tumorigenesis in multiple malignant tumours, including osteosarcoma (OS). Long non-coding RNA Ewing sarcoma-associated transcript 1 (EWSAT1) plays a role in metastasis, and actin cytoskeletal changes in OS remain unclear. In the current study, we showed that EWSAT1 expression was up-regulated in OS and that an elevation in the EWSAT1 expression level was correlated with poor prognosis in patients with OS. Functionally, we showed that knockdown of EWSAT1 suppressed migration and induced actin stress fibre degradation in MNNG/HOS and 143B cells. Moreover, we found that ROCK1 was a key downstream effector in EWSAT1-mediated cell migration and actin stress fibre changes. Furthermore, we demonstrated that ROCK1 and EWSAT1 shared a similar microRNA response element of microRNA-24-3p (miR-24-3p). Moreover, we verified that miR-24-3p suppressed ROCK1 and its mediated migration and actin stress fibres change by direct targeting. EWSAT1 promoted ROCK1-mediated migration and actin stress fibre formation through miR-24-3p sponging. Lastly, through an in vivo study, we demonstrated that EWSAT1 promoted lung metastasis in OS. According to the above-mentioned results, we suggest that EWSAT1 acts as an oncogene and that EWSAT1/miR-24-3p/ROCK1 axial could be a new target in the treatment of OS.

SUBMITTER: Shen D 

PROVIDER: S-EPMC7812296 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Long non-coding RNA EWSAT1 promoted metastasis and actin cytoskeleton changes via miR-24-3p sponging in osteosarcoma.

Shen Dewei D   Liu Yize Y   Liu Yuexin Y   Wang Tao T   Yuan Lin L   Huang Xuyang X   Wang Yong Y  

Journal of cellular and molecular medicine 20201122 2


Non-coding RNAs are closely associated with tumorigenesis in multiple malignant tumours, including osteosarcoma (OS). Long non-coding RNA Ewing sarcoma-associated transcript 1 (EWSAT1) plays a role in metastasis, and actin cytoskeletal changes in OS remain unclear. In the current study, we showed that EWSAT1 expression was up-regulated in OS and that an elevation in the EWSAT1 expression level was correlated with poor prognosis in patients with OS. Functionally, we showed that knockdown of EWSAT  ...[more]

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