Oncotarget

Research Papers:

Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells

Yong Wang _, Yueyang Zhang, Tao Yang, Wei Zhao, Ningning Wang, Pengcheng Li, Xiandong Zeng and Weiguo Zhang

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Oncotarget. 2017; 8:59417-59434. https://doi.org/10.18632/oncotarget.19727

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Abstract

Yong Wang1,*, Yueyang Zhang2,*, Tao Yang3,*, Wei Zhao1,*, Ningning Wang4, Pengcheng Li1, Xiandong Zeng5 and Weiguo Zhang3

1The 4th Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, Shenyang, P. R. China

2Department of Pathology, Liaoning Cancer Hospital & Institute, Shenyang, P. R. China

3Department of Joint Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, P. R. China

4The 2nd Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, P. R. China

5Department of Surgical Oncology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, P. R. China

*These authors have contributed equally to this work

Correspondence to:

Yong Wang, email: WY_landy1116@163.com

Xiandong Zeng, email: ZXD_landy1116@163.com

Keywords: lncRNA MALAT1, miR-144-3p, ceRNA, metastasis and proliferation, osteosarcoma

Received: April 26, 2017    Accepted: June 29, 2017    Published: July 31, 2017

ABSTRACT

Long non-coding RNAs (lncRNAs) are involved in various biological processes and diseases including osteosarcoma. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overly expressed in osteosarcoma. But the function and mechanism it works on in osteosarcoma proliferation and metastasis mediated by Rho associated coiled-coil containing protein kinase 1 (ROCK1) and Rho associated coiled-coil containing protein kinase 2 (ROCK2) remain unclear. In the present study, an elevated MALAT1 was found in osteosarcoma tissues and cell lines, and the elevated MALAT1 was correlated with a poor prognosis in osteosarcoma patients. The functional experiments show that a decreased MALAT1 could remarkably inhibit osteosarcoma cell metastasis and proliferation but induce cell cycle arrest, indicating that MALAT1 functioned as an oncogene in osteosarcoma. Furthermore, we confirmed that MALAT1 and ROCK1/ROCK2 which were targeted by microRNA-144-3p (miR-144-3p) shared the same miR-144-3p combining site. Furthermore, the constructed luciferase assay verified that MALAT1 was a target of miR-144-3p. Additionally, the results of a qRT-PCR demonstrated that MALAT1 and miR-144-3p repressed each other’s expression in a reciprocal manner. Finally, we affirmed that an overexpression of MALAT1 inhibited ROCK1/ROCK2 expression and its mediated metastasis and proliferation by working as a competitive endogenous RNA (ceRNA) via miR-144-3p.

In summary, the findings of this study based on the ceRNA theory, combining the research foundation of miR-144-3p, ROCK1 and ROCK2, taking MALAT1 as a new point of study, provided new insights into molecular level proliferation reversal and metastasis of osteosarcoma.


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