Abstract
BackgroundColorectal 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.MethodsLevels 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.ResultsSignificant 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.ConclusionMALAT1 modulated the sensitivity of Ox through ADAM17 in Ox-resistant CRC cells by sponging miR-324-3p, thus MALAT1 might serve as a novel insight for the therapy of CRC.
Highlights
Colorectal cancer (CRC) is one of the most general malignant tumors
Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and ADAM17 were highly expressed, while miR-324-3p was down regulated in Ox-resistant CRC tissues and cells
Knockdown of MALAT1 could boost the sensitivity of Ox-resistant CRC cells response to Ox. *Correspondence: zotwxx@163.com Department of Abdominal Surgery, Linyi Cancer Hospital, No 6 Lingyuan East Road, Linyi 276001, Shandong, China
Summary
Accumulating evidence implied that long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) participated in the tumorigenesis of CRC. Long non-coding RNAs (lncRNAs) with over than 200 nucleotides can exert the functional effects by modifying and interacting numerous types of genes and proteins through mountainous mechanisms [6, 7], flowed by participating in the fundamental pathogenesis, such as carcinogenesis and cardiovascular diseases [8,9,10]. The function of lncRNAs in cancer progression attracted extensive attentions over the past decades, numerous lncRNAs were identified to be implicated in carcinogenesis by working as oncogenic or tumor suppressor genes [11]. It was necessary to completely understand the function of MALAT1 in the Oxresistance response of CRC cells
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