Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/β-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9)

ABSTRACT

Long non-coding RNA (LncRNA) contributes to the occurrence and development of osteosarcoma (OS), although the underlying mechanism is not clear. In the present study, we showed that lncRNA MRPL23-AS1 was remarkably increased in OS tissues and cell lines. Stable knockdown of MRPL23-AS1 evidently attenuated cell viability and invasive ability, meanwhile inhibited in vivo tumor growth and dissemination. In terms of mechanism, luciferase reporter, RNA pull-down and fluorescence in situ hybridization (FISH) assays showed that MRPL23-AS1 competitively interacted with miR-30b, increasing myosin heavy chain 9 (MYH9) expression, a trans- activator of β-catenin, resulting in the activation of Wnt/β-catenin pathway, thereby promoting OS tumorigenesis and metastasis. Importantly, high MRPL23-AS1 was positively correlated with MYH9, while conversely correlated with miR-30b, suggesting that the regulatory axis of MRPL23-AS1/miR-30b/MYH9 does exist in OS. Clinically, OS patients with high MRPL23-AS1 had larger tumor size, higher stage and easier metastasis than those with low MRPL23-AS1, moreover, MRPL23-AS1 was identified as an adverse prognostic factor for OS survival. In conclusion, our results show that MRPL23-AS1 is a key oncogenic lncRNA in OS, targeting of MRPL23-AS1 may be a promising treatment for OS patients.

GRAPHICAL ABSTRACT

KEYWORDS:

• LncRNA
• MRPL23-AS1
• osteosarcoma
• Wnt/β-catenin signaling
• prognosis

Highlights

1. MRPL23-AS1 is frequently overexpressed in OS and linked to poor prognosis.

2. MRPL23-AS1 promotes OS cell proliferation and invasion both in vitro and in vivo.

3. MRPL23-AS1 acts as a sponge of miR-30b.

4. MRPL23-AS1 regulates the miR-30b/MYH9/Wnt/β-catenin axis

Acknowledgements

None.

Disclosure of interest

The authors report no conflict of interest.

Supplementary material

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