CircRNAs: versatile players and new targets in organ fibrosis

Abstract

Organ fibrosis can occur in virtually all major organs with relentlessly progressive and irreversible progress, ultimately resulting in organ dysfunction and potentially death. Unfortunately, current clinical treatments cannot halt or reverse the progression of fibrosis to end-stage organ failure, and thus, advanced antifibrotic therapeutics are urgently needed. In recent years, a growing body of research has revealed that circular RNAs (circRNAs) play pivotal roles in the development and progression of organ fibrosis through highly diverse mechanisms of action. Thus, manipulating circRNAs has emerged as a promising strategy to mitigate fibrosis across different organ types. In this review, we systemically summarize the current state of knowledge about circRNA biological properties and the regulatory mechanisms of circRNAs. A comprehensive overview of major fibrotic signaling pathways and representative circRNAs that are known to modulate fibrotic signals are outlined. Then, we focus on the research progress of the versatile functional roles and underlying molecular mechanisms of circRNAs in various fibrotic diseases in different organs, including the heart, liver, lung, kidney and skin. Finally, we offer a glimpse into the prospects of circRNA-based interference and therapy, as well as their utilization as biomarkers in the diagnosis and prognosis of fibrotic diseases.

GenX Disturbs the Indicators of Hepatic Lipid Metabolism Even at Environmental Concentration in Drinking Water via PPARα Signaling Pathways

“…48 The development of hepatic fibrosis is known to be difficult to reverse once it has developed, and therefore adaptive recovery in mice does not slow down the development of fibrosis, resulting in a dose-dependent relationship between fibrosis formation and GenX. 49 Consequently, we believe that the reduction of AST, ALP, and SOD levels, the alleviation of inflammation, and the downregulation of many lipid metabolism-related genes at 100 ppm may be strongly related to the adaptive recovery of mice, but this is only a preliminary speculation, and further research is needed to prove the specific reasons. Many experimental models also produce adaptive recovery upon exposure to high concentrations of toxicants.…”

“…A mild inflammatory response was observed in the 100 ppm group, which has been shown to be hepatoprotective and to aid in the recovery of tissues and the re-establishment of homeostasis in the body . The development of hepatic fibrosis is known to be difficult to reverse once it has developed, and therefore adaptive recovery in mice does not slow down the development of fibrosis, resulting in a dose-dependent relationship between fibrosis formation and GenX . Consequently, we believe that the reduction of AST, ALP, and SOD levels, the alleviation of inflammation, and the downregulation of many lipid metabolism-related genes at 100 ppm may be strongly related to the adaptive recovery of mice, but this is only a preliminary speculation, and further research is needed to prove the specific reasons.…”

Hallmarks of cancer resistance

“…Additionally, circRNAs interact with RNA-binding proteins, regulating their activity and influencing downstream signaling pathways involved in drug resistance. 249 Table 3 outlines the ways in which distinct types of ceRNAs participate in the development of resistance to cancer treatments.…”

Circular RNA circ_0003609 ameliorates hypertrophied ligamentum flavum by regulating the miR-155/SIRT1 axis

“…Circular RNAs (circRNAs), which are classified as noncoding RNA, exploit covalent bonds to form closed-loop structures [3,4]. Studies showed that circRNAs significantly impact the progression of fibrotic diseases [5][6][7]. The study of Zhang et al demonstrated that circPDK1 promoted the propagation, dissemination, and fibrosis of LF cells [7].…”