RNA-binding protein (RBP) has a highly dynamic spatiotemporal regulation process and important biological functions. They are critical to maintain the transcriptome through post-transcriptionally controlling the processing and transportation of RNA, including regulating RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation. Alteration of each process will affect the RNA life cycle, produce abnormal protein phenotypes, and thus lead to the occurrence and development of tumors. Here, we summarize RBPs involved in tumor progression and the underlying molecular mechanisms whereby they are regulated and exert their effects. This analysis is an important step towards the comprehensive characterization of post-transcriptional gene regulation involved in tumor progression.

Background: Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness. Methods: Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. Results: MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. Conclusion: MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.

Iron is an essential trace element for the human body, and its deficiency or excess can induce a variety of biological processes. Plenty of evidences have shown that iron metabolism is closely related to the occurrence and development of tumors. In addition, iron plays an important role in cell death, which is very important for the development of potential strategies for tumor treatment. Here, we reviewed the latest research about iron metabolism disorders in various types of tumors, the functions and properties of iron in ferroptosis and ferritinophagy, and new opportunities for iron-based on treatment methods for tumors, providing more information regarding the prevention and treatment of tumors.

Cancer stem cells (CSCs) contribute to the initiation, recurrence, and metastasis of cancer; however, there are still no drugs targeting CSCs in clinical application. There are several signaling pathways playing critical roles in CSC progression, such as the Wnt, Hedgehog, Notch, Hippo, and autophagy signaling pathways. Additionally, targeting the ferroptosis signaling pathway was recently shown to specifically kill CSCs. Therefore, targeting these pathways may suppress CSC progression. The structure of small-molecule drugs shows a good spatial dispersion, and its chemical properties determine its good druggability and pharmacokinetic properties. These characteristics make small-molecule drugs show a great advantage in drug development, which is increasingly popular in the market. Thus, in this review, we will summarize the current researches on the small-molecule compounds suppressing CSC progression, including inhibitors of Wnt, Notch, Hedgehog, and autophagy pathways, and activators of Hippo and ferroptosis pathways. These small-molecule compounds emphasize CSC importance in tumor progression and propose a new strategy to treat cancer in clinic via targeting CSCs.