Post-transcriptional regulation of cytokine and growth factor signaling in cancer

Abstract

Cytokines and growth factors regulate cell proliferation, differentiation, migration and apoptosis, and play important roles in coordinating growth signal responses during development. The expression of cytokine genes and the signals transmitted through cytokine receptors are tightly regulated at several levels, including transcriptional and post-transcriptional levels. A majority of cytokine mRNAs, including growth factor transcripts, contain AU-rich elements (AREs) in their 3’ untranslated regions that control gene expression by regulating mRNA degradation and changing translational rates. In addition, numerous proteins involved in transmitting signals downstream of cytokine receptors are regulated at the level of mRNA degradation by GU-rich elements (GREs) found in their 3’ untranslated regions. Abnormal stabilization and overexpression of ARE or GRE-containing transcripts had been observed in many malignancies, which is a consequence of the malfunction of RNA-binding proteins. In this review, we briefly summarize the role of AREs and GREs in regulating mRNA turnover to coordinate cytokine and growth factor expression, and we describe how dysregulation of mRNA degradation mechanisms contributes to the development and progression of cancer.

Effect of m6A RNA Methylation Regulators on Malignant Progression and Prognosis in Renal Clear Cell Carcinoma

“…Several biological processes and pathways correlated with the tumorigenesis and progression of ccRCC were identified including "cytokine-cytokine receptor interaction, " "cell adhesion molecules (CAMs), " "complement and coagulation cascades, " "leukocyte migration, " "regulation of leukocyte activation, " "regulation of immune effector process, " and so on. It was known that the expression or function of cytokines, including cellular self-renewal, senescence, migration, and apoptosis was often altered in tumor tissues compared with healthy tissues (52)(53)(54). CAMs was found to promote the metastasis of head and neck squamous cell carcinoma via detaching the tumor cells from primary tumor and decreasing the intercellular adhesion (55).…”

Dysregulation of tristetraprolin and human antigen R promotes gastric cancer progressions partly by upregulation of the high-mobility group box 1

“…The progression of mRNAs through splicing, maturation, transportation, localization, and degradation is tightly controlled by post-transcriptional regulatory factors, including miRNAs, long non-coding RNAs, RNA-binding proteins and other factors 27 . Transcripts of a lot of cytokines, chemokines, growth factors, and so on are highly enriched of AREs, which interact with ARE-BPs to regulate the stability and translation of these mRNAs 28 . Mutations in binding regions, dysregulation of ARE-BPs expression, aberrant interplay networks with miRNAs and other factors may alter the interaction between ARE-BPs and ARE-containing transcripts and result in elevated expressions of tumor-promoting targets 27 .…”

Biology of RNA Surveillance in Development and Disease

“…AU-rich elements (AREs) interact with RBPs that regulate the processing and decay of mRNAs [28]. GU-rich elements are found in genes of signaling components and are upregulated in cancer cells [29]. 3′ untranslated region (UTR) miRNA binding sites are crucial for gene expression regulation and RNAi.…”