MALAT-1 is Associated with the Doxorubicin Resistance in U-2OS Osteosarcoma Cells

Abstract

Purpose

Our study aimed to investigate the relationship between MALAT-1 (metastasis-associated lung adenocarcinoma transcript 1) expression and the chemotherapy drug resistance in osteosarcoma.

Methods

The U-2OS osteosarcoma cell line was selected for the experiment. The cells were treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, respectively. RT-PCR was applied to detect the MALAT-1 expression in cells. The doxorubicin-resistant cell line was constructed. The cells were divided into doxorubicin-sensitivity group (DS/shCtrl), doxorubicin-resistance group (DR/shCtrl) and shMALAT1-doxorubicin-resistance group (DR/shMALAT1). The colony formation assay and 5-ethynyl-2ʹ-deoxyuridine (EdU) assay were used to detect cell proliferation. PI staining was used to detect the cell cycle. Transwell assay and wound healing assay were used to observe the migration and invasion ability. Annexin V-FITC assay was used to detect cell apoptosis. Western blot was used to detect the protein expression and potential mechanism. The impacts of MALAT-1 expression were verified in vivo.

Results

The MALAT-1 was upregulated in the doxorubicin-resistant U-2OS osteosarcoma cells. Downregulating MALAT-1 in the doxorubicin-resistant cells inhibited the proliferation, migration, and invasiveness, increased the ratio of cells in the G0/G1 phase, promoted apoptosis. In the doxorubicin-resistant U-2OS cells, the extracellular regulated protein kinases (ERK) phosphorylation was declined, which could be reversed by downregulating MALAT-1. In vivo assay indicated that the growth of doxorubicin-resistant solid osteosarcoma could be suppressed by downregulating MALAT-1.

Conclusion

Our study provides evidence that doxorubicin may upregulate MALAT-1 in osteosarcoma. Downregulating MALAT-1 in the doxorubicin resistance U-2OS cells could reverse the resistance and may improve chemotherapeutic efficiency. Some conclusions in previous literature may be one-sided.

Keywords:

• osteosarcoma
• doxorubicin
• long noncoding RNA
• MALAT-1
• chemotherapy resistance
• extracellular regulated protein kinases

Acknowledgments

This work was supported by The 900th Hospital Project (No. 2018Q08, to Chang Liu), and “234 Subject Peak Climbing Plan” of The First Hospital Affiliated to the Naval Medical University (No. 2019YXK055, to Zhiwei Wang).

Disclosure

The authors report no conflicts of interest in this work.