Long non-coding RNA MALAT1 regulates oxaliplatin-resistance via miR-324-3p/ADAM17 axis in colorectal cancer cells
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PRIMARY RESEARCH
Cancer Cell International Open Access
Long non‑coding RNA MALAT1 regulates oxaliplatin‑resistance via miR‑324‑3p/ADAM17 axis in colorectal cancer cells Changru Fan, Qiulan Yuan, Guifeng Liu, Yuliang Zhang, Maojun Yan, Qingxu Sun and Chaoyu Zhu*
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 (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 CRC cells by sponging miR324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC. Keywords: MALAT1, miR-324-3p, ADAM17, Ox-sensitivity, CRC Highlights 1. MALAT1 and ADAM17 were highly expressed, while miR-324-3p was down regulated in Ox-resistant CRC tissues and cells. 2. Knockdown of MALAT1 could boost the sensitivity of Ox-resistant CRC cells response to Ox.
*Correspondence: [email protected] Department of Abdominal Surgery, Linyi Cancer Hospital, No. 6 Lingyuan East Road, Linyi 276001, Shandong, China
3. Either miR-324-3p inhibition or ADAM17 increase could abolish the effect of MALAT1 deletion on Oxsensitivity in vitro. 4. MALAT1 regulated the tumorigenesis via miR324-3p/ADAM17 axis in Ox-treated mice.
Background Colorectal cancer (CRC) is one of the leading causes which contributed to cancer-related deaths, and more than 1.2 million new cases of CRC are diagnosed every year all over the world [1, 2]. Recently, oxaliplatin
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