Long noncoding RNA MALAT1 affects the efficacy of radiotherapy for esophageal squamous cell carcinoma by regulating Cks1 expression

Objective: Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been well studied in the progression of many malignancies. However, its association with the radioresistance of tumors has not been well understood yet. This study tried to explore the role of MALAT1 in regulating the radiosensitivity of esophageal cancer (EC), especially esophageal squamous cell carcinoma (ESCC), involving its regulation on Cks1 expression.

Methods: KYSE150 cells were subcutaneously inoculated into nude mice to establish ESCC xenografts. Real-time PCR and Western blot analysis were performed to detect the expression of MALAT1 and Cks1 in irradiated xenografts and cells. Functional analysis was performed in both EC9706 and KYSE150 cells via the transfection of corresponding plasmids or small interfering RNAs (siRNAs). Irradiation-induced damage was examined by the detection of cell viability and apoptosis using MTT and TUNEL assays, respectively.

Results: Both MALAT1 and Cks1 were downregulated in irradiated xenografts and cells. Cks1FER1L4 showed significant downregulation. Overexpression of MALAT1 inhibited irradiation-induced decrease in cell viability, increase in apoptosis, and downregulation of Cks1. Cks1 expression was also downregulated by MALAT1 siRNA, while Cks1 siRNA strongly recovered MALAT1-induced radioresistance in vitro. Moreover, better tumor growth, accompanied by Cks1 upregulation, was observed in KYSE150 xenografts with MALAT1 overexpression, especially under radiation treatment.

Conclusion: MALAT1 acted as one positive regulator of the radioresistance of ESCC, at least partly due to its promotion on Cks1 expression. Furthermore, MALAT1-targeted therapies showed great potential in enhancing the radiotherapeutic effect on ESCC.