Journal
MOLECULAR THERAPY
Volume 26, Issue 6, Pages 1494-1508Publisher
CELL PRESS
DOI: 10.1016/j.ymthe.2018.04.002
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Funding
- National Natural Science Foundation of China [81672676, 81472521, 81272951, 81602379]
- Guangdong Provincial Natural Science Foundation [2017A030311011]
- Specialized Research Fund for the Doctoral Program of Higher Education [20110171110068]
- Science and Technology Project of Guangzhou City [2012J4100078]
- China Post-doctoral Science Foundation [2016M590839]
- Fundamental Research Funds for the Central Universities [13ykpy27]
- Fund for Excellent Doctoral Dissertation of Guangdong Province [SYBZZXM201304]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013]163]
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes [K1809001]
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Increasing evidence has shown that chemo-resistance is related to the process of epithelial-mesenchymal transition (EMT) and increased invasiveness by tongue squamous cell carcinoma (TSCC) cells. Long non-coding RNAs (lncRNAs) play pivotal roles in tumor metastasis and progression. However, the roles and mechanisms of lncRNAs in cisplatin-resistance-induced EMT and metastasis are not well understood. In this study, a chemotherapy-induced lncRNA 1 (CILA1) was discovered by using microarrays and was functionally identified as a regulator of chemo-sensitivity in TSCC cells. Upregulation of CILA1 promotes EMT, invasiveness, and chemo-resistance in TSCC cells, whereas the inhibition of CILA1 expression induces mesenchymal-epithelial transition (MET) and chemosensitivity, and inhibits the invasiveness of cisplatin-resistant cells both in vitro and in vivo. We also found that CILA1 exerts its functions via the activation of the Wnt/beta-catenin signaling pathway. High CILA1 expression levels and low levels of phosphorylated beta-catenin were closely associated with cisplatin resistance and advanced disease stage, and were predictors of poor prognosis in TSCC patients. These findings provided a new biomarker for the chemo-sensitivity of TSCC tumors and a therapeutic target for TSCC treatment.
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