Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells

Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells

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Abstract Background Colorectal cancer (CRC) is one of the most general malignant tumors.Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC.However, the effect of MALAT1 in drug-resistance needed to be further illustrated.

Methods Levels of MALAT1, microRNA (miR)-324-3p, and a disintegrin and metalloprotease metallopeptidase domain 17 (ADAM17) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay.Cell Counting Kit 8 (CCK-8) was used to assess the half maximal inhibitory concentration miracle academy clothing (IC50) of oxaliplatin (Ox).Meanwhile, cell proliferation, migration and apoptosis were detected by CCK-8, transwell assay, and flow cytometry, respectively.

The interaction between miR-324-3p and MALAT1 or ADAM17 was clarified by dual-luciferase reporter assay.Also, the effect of MALAT1 on tumor growth was detected in xenograft tumor mice treated with Ox.Results Significant up regulation of MALAT1 and ADAM17, and decrease of miR-324-3p were observed in Ox-resistant CRC tissues and cells.

MALAT1 deficiency enhanced the sensitivity of Ox-resistant CRC cells response to Ox, while miR-324-3p repression or ADAM17 acceleration could overturn this effect.Moreover, MALAT1 silencing repressed tumor growth in Ox-treated nude mice.Mechanically, MALAT1 exerted promotion effect on the resistance response to Ox via miR-324-3p/ADAM17 axis in Ox-resistant CRC cells.

Conclusion MALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant here CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.