Quercetin Affects Carcinogenic Phenotype of Breast and Lung Cancer Cells Differentially Through Sterol Regulation Mediated by MALAT1 Perturbation.

Targeting MALAT1 in cancer treatment is an attractive strategy due to the undebatable role of this lncRNA in the disease. Small molecules toward this noncoding RNA have, in fact, entered preclinical trials, without resulting in a robust demonstration in favor of their use in therapy. To test the robustness of this method, we asked how aspects of carcinogenesis get affected when knocking down MALAT1 in different cell lines. Using two such cell lines in this study to compare side-by-side, we observed that small molecule quercetin (and its subsequent reduction of MALAT1 lncRNA levels) showed heterogenic effects on carcinogenesis, which is similarly indicated by previous literature. Further, using a combination of cell biology (including the use of 3D tumor spheroids) and bioinformatics, this study is able to pinpoint the probable function of the SREBP1 protein (which showed a significant reduction of around 50%) in affecting carcinogenesis via MALAT1, corroborating earlier reports that link MALAT1 to the sterol regulation axis. This study, in summary, notes that using MALAT1 reduction (using quercetin or otherwise) needs to be very specific in the targeting of cancer cells in order to avoid paradoxical results.