miR-802 regulates human angiotensin II type 1 receptor expression in intestinal epithelial C2BBe1 cells

Abstract

Studies have demonstrated that angiotensin II (Ang II) can regulate intestinal fluid and electrolyte transport and control intestinal wall muscular activity. Ang II is also a proinflammatory mediator that participates in inflammatory responses such as apoptosis, angiogenesis, and vascular remodeling; accumulating evidence suggests that this hormone may be involved in gastrointestinal (GI) inflammation and carcinogenesis. Ang II binds to two distinct G protein-coupled receptor subtypes, the AT(1)R and AT(2)R, which are widely expressed in the GI system. Together these studies suggest that Ang II-AT(1)R/-AT(2)R actions may play an important role in GI tract physiology and pathophysiology. Currently it is not known whether miRNAs can regulate the expression of the human AT(1)R (hAT(1)R) in the GI system. PCR and in situ hybridization experiments demonstrated that miR-802 was abundantly expressed in human colon and intestine. Luciferase reporter assays demonstrated that miR-802 could directly interact with the bioinformatics-predicted target site harbored within the 3'-untranslated region of the hAT(1)R mRNA. To validate that the levels of miR-802 were physiologically relevant in the GI system, we demonstrated that miR-802 "loss-of-function" experiments resulted in augmented hAT(1)R levels and enhanced Ang II-induced signaling in a human intestinal epithelial cell line. These results suggest that miR-802 can modulate the expression of the hAT(1)R in the GI tract and ultimately play a role in regulating the biological efficacy of Ang II in this system.

The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells

“…The results show that DLC1 , ATRX and HFE genes are regulated by miR-200a and miR-200c; DLC1 , HFE and HNRNPA3 are regulated by miR-200b. Although, the changes in the expression of these genes at the mRNA and protein levels after re-expression of miR-200s in H1299 cells were relatively small (<2-fold), such small changes in the expression of microRNA targets are very common (16,53). Despite restoration of normal miR-200 levels, some other components of the post-transcriptional gene silencing pathway in H1299 cells might be in limiting amounts, for example Dicer, which is commonly downregulated in cancer cells (54).…”

MiR‐802 causes nephropathy by suppressing NF‐κB‐repressing factor in obese mice and human

“…MiR‐802 was identified as an important mediator in controlling different pathological process. Intestinal miR‐802 affected the biological efficacy of angiotensin II in gastrointestinal system . In obesity, up‐regulated hepatic miR‐802 impaired glucose metabolism through silencing of Hnf1b .…”

microRNA-802 promotes lung carcinoma proliferation by targeting the tumor suppressor menin

“…In the present study, miR-802 was characterized as an miRNA that has an important role in the development of lung carcinoma. A previous study demonstrated that miR-802 modulates the biological efficacy of angiotensin II (Ang II) in the human gastrointestinal tract through regulation of the Ang II type 1 receptor expression (14). Furthermore, Kornfeld et al (15) demonstrated that the deregulated expression of miR-802 has a critical role in the development of the obesity-associated impairment of glucose metabolism through targeting of hepatocyte nuclear factor-1β (14).…”