Lung cancer is the most devastating malignancy in the world. Beyond genetic research, epigenomic studies—especially investigations of microRNAs—have grown rapidly in quantity and quality in the past decade. This has enriched our understanding about basic cancer biology and lit up the opportunities for potential therapeutic development. In this review, we summarize the involvement of microRNAs in lung cancer carcinogenesis and behavior, by illustrating the relationship to each cancer hallmark capability, and in addition, we briefly describe the clinical applications of microRNAs in lung cancer diagnosis and prognosis. Finally, we discuss the potential therapeutic use of microRNAs in lung cancer.

unpaired (upd) encodes a ligand for the Jak/STAT signaling pathway in Drosophila. In the second instar and early third larval eye disc, upd is expressed in the center of the posterior margin. upd loss-of-function mutations caused eye size reduction and upd overexpression caused eye enlargement. Upd regulates eye size through the Dome/Jak(Hop)/STAT92 signaling pathway to promote cell proliferation. Interestingly, the effect of Upd is only on cells located anterior to the morphogenetic furrow (MF), but has no effect on the second mitotic wave, which is posterior to MF. Overexpression of upd behind MF can nonautonomously induce cell proliferation up to 20 rows of cells anterior to MF. The G1 cyclin, cycD transcript level was also enhanced anterior to MF. Consistent with the long-range effect, we found that the extracellular Upd protein can be detected over a comparable long range, suggesting that Upd acts directly over a long distance as a signaling molecule.

SummaryThe Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is involved in the regulation of intestinal stem cell (ISC) activity to ensure a continuous renewal of the adult Drosophila midgut. Three ligands, Unpaired 1, Unpaired 2 and Unpaired 3 (Upd1, Upd2 and Upd3, respectively) are known to activate the JAK/STAT pathway in Drosophila. Using newly generated upd mutants and cell-specific RNAi, we showed that Upd1 is required throughout the fly life to maintain basal turnover of the midgut epithelium by controlling ISC maintenance in an autocrine manner. A role of Upd2 and Upd3 in basal conditions is discernible only in old gut, where they contribute to increased ISC abnormal division. Finally, upon an acute stress such as oral bacterial infection, we showed that Upd3 is released from enterocytes and has an additive effect with Upd2 to promote rapid epithelial regeneration. Taken together, our results show that Upd ligands are required to maintain the midgut homeostasis under both normal and pathological states.

Notch (N) signal is activated at the dorsoventral (DV)border of the Drosophila eye disc and is important for growth of the eye disc. In this study, we showed that the Pax protein Eyg is a major effector mediating the growth promotion function of N. eyg transcription is induced by N signaling occurring at the DV border. Like N, eyg controls growth of the eye disc. Loss of N signaling can be compensated by overexpressing eyg, whereas loss of the downstream eyg blocked the function of N signaling. In addition, we showed that N and eyg could induce expression of upd, which encodes the ligand for the Jak/STAT pathway and acts over long distance to promote cell proliferation. Loss of eyg or N can be compensated by overexpressing upd. These results suggest that upd is a major effector mediating the function of eyg and N. The functional link from N to eyg to upd explains how the localized Notch activation can achieve global growth control.