Metastasis is a multistep process beginning with the dissemination of tumor cells from a primary site and leading to secondary tumor development in an anatomically distant location. Although significant progress has been made in understanding the molecular characteristics of metastasis, many questions remain regarding the intracellular mechanisms governing transition through the various metastatic stages. Long non-coding RNAs (lncRNAs) are capable of modulating both transcriptional and post-transcriptional regulation, and thus, coordinating a wide array of diverse cellular processes. Current evidence indicates that lncRNAs may also play a crucial role in the metastatic process through regulation of metastatic signaling cascades as well as interaction with specific metastatic factors. Here we summarize a subset of lncRNAs with proposed roles in metastasis and, when applicable, highlight the mechanism by which they function.

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BackgroundDrug screening for the identification of compounds with anticancer activity is commonly performed using cell lines cultured under normal oxygen pressure and physiological pH. However, solid tumors are characterized by a microenvironment with limited access to nutrients, reduced oxygen supply and acidosis. Tumor hypoxia and acidosis have been identified as important drivers of malignant progression and contribute to multicellular resistance to different forms of therapy. Tumor acidosis represents an important mechanism mediating drug resistance thus the identification of drugs active on acid-adapted cells may improve the efficacy of cancer therapy.MethodsHere, we characterized human colon carcinoma cells (HCT116) chronically adapted to grow at pH 6.8 and used them to screen the Prestwick drug library for cytotoxic compounds. Analysis of gene expression profiles in parental and low pH-adapted cells showed several differences relating to cell cycle, metabolism and autophagy.ResultsThe screen led to the identification of several compounds which were further selected for their preferential cytotoxicity towards acid-adapted cells. Amongst 11 confirmed hits, we primarily focused our investigation on the benzoporphyrin derivative Verteporfin (VP). VP significantly reduced viability in low pH-adapted HCT116 cells as compared to parental HCT116 cells and normal immortalized epithelial cells. The cytotoxic activity of VP was enhanced by light activation and acidic pH culture conditions, likely via increased acid-dependent drug uptake. VP displayed the unique property to cause light-dependent cross-linking of proteins and resulted in accumulation of polyubiquitinated proteins without inducing inhibition of the proteasome.ConclusionsOur study provides an example and a tool to identify anticancer drugs targeting acid-adapted cancer cells.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0645-5) contains supplementary material, which is available to authorized users.

The microRNA-34a is a well-studied tumor suppressor microRNA (miRNA) and a direct downstream target of TP53 with roles in several pathways associated with oncogenesis, such as proliferation, cellular growth, and differentiation. Due to its broad tumor suppressive activity, it is not surprising that miR34a expression is altered in a wide variety of solid tumors and hematological malignancies. However, the mechanisms by which miR34a is regulated in these cancers is largely unknown. In this study, we find that a long noncoding RNA transcribed antisense to the miR34a host gene, is critical for miR34a expression and mediation of its cellular functions in multiple types of human cancer. We name this long noncoding RNA lncTAM34a, and characterize its ability to facilitate miR34a expression under different types of cellular stress in both TP53-deficient and wild-type settings.

Supplementary data are available at Bioinformatics online.