microRNA‐495 reduces visceral sensitivity in mice with diarrhea‐predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB

Abstract

Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is one of the most common gastrointestinal disorders in the world, lacking effective therapies. The crucial roles of microRNAs (miRNAs) in IBS‐D have attracted increasing attention. The aim of this study is to investigate the effects of miR‐495 on the visceral sensitivity of the IBS‐D through the PI3K/AKT signaling pathway by targeting PKIB. Microarray data analysis was employed to screen the differentially expressed genes related to IBS‐D and regulatory miRNAs. Then, mice were perfused with acetic acid into the rectum to establish the IBS‐D model. Next, PKIB expression was measured in IBS‐D mice. Additionally, model mice were injected with a series of adenovirus vector to investigate the influence of miR‐495 on visceral sensitivity and rectal function in IBS‐D mice with the involvement of PKIB and PI3K/AKT signaling pathway. The IBS‐D mouse model was successfully established. PKIB was the target gene of miR‐495, and highly expressed in mice with IBS‐D. Silencing PKIB reduced visceral sensitivity in mice with IBS‐D, and overexpression of miR‐495 decreased visceral sensitivity in mice with IBS‐D by inhibiting PKIB. Moreover, miR‐495 upregulation inhibited PI3K/AKT signaling pathway through downregulating PKIB. To sum up, this study reveals that miR‐495 upregulation can reduce visceral sensitivity in IBS‐D via inhibition of PI3K/AKT signaling pathway by targeting PKIB. It suggests that miR‐495 presents a potential target for IBS‐D therapy.

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

“…It said that CT is able to induce epigenetic alterations in disease therapy. MicroRNAs (miRs) are short endogenous non‐coding RNAs that participate in expression regulation and do not encode into protein (Fei & Wang, 2020). MiR dysregulation has been implicated in different diseases (Farooqi et al, 2019; Lu, Weng, Li, Yang, & Qian, 2020).…”

Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice

“…The PI3K–Akt signaling pathway is reportedly related to various diverse physiological stresses. It plays a crucial regulatory role during cellular stress ( 39 – 41 ) and is reportedly associated with stress-induced diarrhea, predominantly IBS (IBS-D), and UC ( 38 , 42 – 44 ). In addition, the results of KEGG enrichment analysis show that the PI3K–Akt signaling pathway (number of enriched genes = 39) can enrich more genes than the TNF signaling pathway (number of enriched genes = 23).…”

Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network in Human Diarrhea Irritable Bowel Syndrome

“…The Phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (AKT) pathway is an important pathway in the regulation of cell proliferation and apoptosis [29] . Akt is a serine/threonine kinase and an important target of PI3K.Fei and WANG's [30] study revealed that miR-495 upregulation can reduce visceral sensitivity in IBS-D via inhibition of PI3K/AKT signaling pathway by targeting PKIB.SONG et al [31] found overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process through inhibition of the PI3K/AKT signaling pathway, but promoted apoptosis of GC cells.…”