Long non‐coding RNAs and TGF‐β signaling in cancer

Cancer is driven by genetic mutations in oncogenes and tumor suppressor genes and by cellular events that develop a misregulated molecular microenvironment in the growing tumor tissue. The tumor microenvironment is guided by the excessive action of specific cytokines including transforming growth factor‐β (TGF‐β), which normally controls embryonic development and the homeostasis of young or adult tissues. As a consequence of the genetic alterations generating a given tumor, TGF‐β can preserve its homeostatic function and attempt to limit neoplastic expansion, whereas, once the tumor has progressed to an aggressive stage, TGF‐β can synergize with various oncogenic stimuli to facilitate tumor invasiveness and metastasis. TGF‐β signaling mechanisms via Smad proteins, various ubiquitin ligases, and protein kinases are relatively well understood. Such mechanisms regulate the expression of genes encoding proteins or non‐coding RNAs. Among non‐coding RNAs, much has been understood regarding the regulation and function of microRNAs, whereas the role of long non‐coding RNAs is still emerging. This article emphasizes TGF‐β signaling mechanisms leading to the regulation of non‐coding genes, the function of such non‐coding RNAs as regulators of TGF‐β signaling, and the contribution of these mechanisms in specific hallmarks of cancer.