Knockdown of Linc00515 Inhibits Multiple Myeloma Autophagy and Chemoresistance by Upregulating miR-140-5p and Downregulating ATG14

Linc00515 的敲低通过上调 miR-140-5p 和下调 ATG14 抑制多发性骨髓瘤自噬和化学耐药性

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作者:Daifeng Lu, Chuandong Yang, Zhitao Zhang, Yu Cong, Mochao Xiao

Aims

The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells.

Background/aims

The purpose of our experiments was to investigate the targeting relationship of linc00515, miR-140-5p and ATG14 and to explore the roles of linc00515, miR-140-5p and ATG14 in autophagy and chemoresistance of melphalan-resistant multiple myeloma cells.

Conclusion

Linc00515 enhanced autophagy and chemoresistance of melphalan-resistant myeloma by directly inhibiting miR-140-5p, which elevated ATG14 level.

Methods

Plasmids that could interfere with the expression of linc00515 and ATG14 were loaded into myeloma cells, which were cultured with melphalan. MTT assay and flow cytometry analysis were utilized to investigate the effect of linc00515, miR-140-5p and ATG14 on the resistance of myeloma cells. QRT-PCR was used to determine the levels of mRNAs. Western blot was utilized to explore the level of ATG14 and autophagy-related proteins. Dual luciferase assay was utilized to explore the targeting relationship between linc00515, miR-140-5p and ATG14. GFP LC3 fluorescence assay was conducted to study the autophagy of cells.

Results

The expression of linc00515 and ATG14 were significantly higher in melphalan-resistant myeloma cells. Knockdown of linc00515 and ATG14 led to decreased autophagy and chemoresistance of melphalan-resistant myeloma cells. The forced expression of miR-140-5p suppressed autophagy and chemoresistance of melphalan-resistant myeloma cells.

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