Zhengyi Bao

Tryptophan (Trp) metabolism primarily involves the kynurenine, 5-hydroxytryptamine, and indole pathways. A variety of bioactive compounds produced via Trp metabolism can regulate various physiological functions, including inflammation, metabolism, immune responses, and neurological function. Emerging evidence supports an intimate relationship between Trp metabolism disorder and diseases. The levels or ratios of Trp metabolites are significantly associated with many clinical features. Additionally, studies have shown that disease progression can be controlled by modulating Trp metabolism. Indoleamine-2,3-dioxygenase, Trp-2,3-dioxygenase, kynurenine-3-monooxygenase, and Trp hydroxylase are the rate-limiting enzymes that are critical for Trp metabolism. These key regulatory enzymes can be targeted for treating several diseases, including tumors. These findings provide novel insights into the treatment of diseases. In this review, we have summarized the recent research progress on the role of Trp metabolites in health and disease along with their clinical applications.

The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT-related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.

Abstract Cancer is one of the major diseases threatening human life and health worldwide. Epigenetic modification refers to heritable changes in the genetic material without any changes in the nucleic acid sequence and results in heritable phenotypic changes. Epigenetic modifications regulate many biological processes, such as growth, aging, and various diseases, including cancer. With the advancement of next-generation sequencing technology, the role of RNA modifications in cancer progression has become increasingly prominent and is a hot spot in scientific research. This review studied several common RNA modifications, such as N 6 -methyladenosine, 5-methylcytosine, and pseudouridine. The deposition and roles of these modifications in coding and noncoding RNAs are summarized in detail. Based on the RNA modification background, this review summarized the expression, function, and underlying molecular mechanism of these modifications and their regulators in cancer and further discussed the role of some existing small-molecule inhibitors. More in-depth studies on RNA modification and cancer are needed to broaden the understanding of epigenetics and cancer diagnosis, treatment, and prognosis.

CircRNAs, covalently closed noncoding RNAs, are widely expressed in a wide range of species ranging from viruses to plants to mammals. CircRNAs were enriched in the Wnt pathway. Aberrant Wnt pathway activation is involved in the development of various types of cancers. Accumulating evidence indicates that the circRNA/Wnt axis modulates the expression of cancer-associated genes and then regulates cancer progression. Wnt pathway-related circRNA expression is obviously associated with many clinical characteristics. CircRNAs could regulate cell biological functions by interacting with the Wnt pathway. Moreover, Wnt pathway-related circRNAs are promising potential biomarkers for cancer diagnosis, prognosis evaluation, and treatment. In our review, we summarized the recent research progress on the role and clinical application of Wnt pathway-related circRNAs in tumorigenesis and progression.