Knockdown of MALAT1 inhibits osteosarcoma progression via regulating the miR‑34a/cyclin D1 axis

Duan,Guangchao; Zhang,Chuanlin; Xu,Changke; Xu,Chao; Zhang,Lei; Zhang,Yan

doi:10.3892/ijo.2018.4600

Knockdown of MALAT1 inhibits osteosarcoma progression via regulating the miR‑34a/cyclin D1 axis

Authors:
- Guangchao Duan
- Chuanlin Zhang
- Changke Xu
- Chao Xu
- Lei Zhang
- Yan Zhang
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Affiliations: Department of Spine Surgery, Shangqiu First People's Hospital, Shangqiu, Henan 476100, P.R. China
Published online on: October 19, 2018 https://doi.org/10.3892/ijo.2018.4600
Pages: 17-28
Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding (lnc)RNAs have been demonstrated to be involved in the development of various types of cancers, such as osteosarcoma (OS). Long non‑coding (lnc)RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) expression was reported to be highly expressed in OS and promoted the development of this disease; however, the underlying molecular mechanism by which MALAT1 promotes the progression of OS requires further investigation. In the present study, the expression of MALAT1 and miR‑34a was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The abundance of cyclin D1 (CCND1) was detected by RT‑qPCR and western blotting. Cell viability, migration and invasion were examined by MTT and Transwell assays. The interaction between miR‑34a and MALAT1 or CCND1 was probed by a dual luciferase reporter assay and RNA immunoprecipitation. Xenograft tumor assay was performed to verify the roles of MALAT1 and miR‑34a in tumor growth in vivo. The results demonstrated that MALAT1 and CCND1 mRNA expression levels were upregulated and miR‑34a was downregulated in OS tissues and cells. Additionally, MALAT1 expression was correlated with tumor size, clinical stage and distant metastasis in patients with OS. In addition, MALAT1 promoted OS cell viability, invasion and migration, while MALAT1 silencing exhibited opposing effects. Moreover, MALAT1 functioned as a ceRNA to suppress miR‑34a expression and in turn upregulate CCND1 in OS cells. Rescue experiments further demonstrated that MALAT1 knockdown partially reversed anti‑miR‑34a‑mediated promotion on OS cell viability, migration and invasion; overexpression of CCND1 partially reversed the effects of MALAT1 silencing on OS progression. Furthermore, in vivo experiments also revealed that MALAT1 promoted OS tumor growth via miR‑34a inhibition and upregulating the expression of CCND1. In conclusion, the present study suggested that MALAT1 exerted its oncogenic function in OS by regulating the miR‑34a/CCND1 axis in OS, which may provide novel insight into the diagnosis and therapy for OS.

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