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.

Highlights

  • As the most prevalent primary malignant tumor in adolescents, osteosarcoma is always regarded as one of the main reasons for cancer-related deaths in children and young adolescents [1,2,3]

  • Long non-coding RNAs, which are a group of RNAs that measure more than 200 nucleotides in length, have become the focus in numerous types of cellular processes including the modulation of cell proliferation, apoptosis and invasion, the reprogramming of stem cell differentiation and chromatin remodeling [7,8,9,10]

  • It is widely reported that Long non-coding RNAs (lncRNAs) involved in multiple malignant tumors including osteosarcoma [2832]

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Summary

Introduction

As the most prevalent primary malignant tumor in adolescents, osteosarcoma is always regarded as one of the main reasons for cancer-related deaths in children and young adolescents [1,2,3]. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), referred to as nuclearenriched abundant transcript 2 (NEAT2), is one of the first discovered cancer-associated lncRNAs [11,12,13]. It is an evolutionarily highly conserved and widely expressed long noncoding transcript with a length of 8,000 nucleotides. Deregulation or a functional role for MALAT1 has been established in several solid tumors, including lung cancer, breast cancer, hepatocellular carcinoma, prostate cancer and gallbladder cancer [14,15,16,17]. The functional roles of MALAT1 in the tumorigenesis and progression of osteosarcoma have not been extensively studied

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