Effect of metformin on the long non-coding RNA expression levels in type 2 diabetes: an in vitro and clinical trial study.

BACKGROUND: It has been suggested that the anti-hyperglycemic effect of metformin could be associated with its impact on long non-coding RNA (lncRNA) expression levels. Accordingly, in the current study, we evaluated the effect of metformin on the expression of H19, MEG3, MALAT1, and GAS5 in in vitro and in vivo situations. METHODS: The effect of hyperglycemia and metformin treatment on the lncRNAs expression level was evaluated in HepG2 cells. A total of 179 age- and sex-matched subjects, including 88 newly diagnosed patients with type 2 diabetes (T2D) and 91 healthy volunteers, were included in the case-control phase of the study. Moreover, 40 newly diagnosed patients participated in the study's open-labeled non-controlled clinical trial phase. The expression levels of lncRNA in HepG2 cells and whole blood samples were determined using QRT-PCR. RESULTS: In vitro results showed that hyperglycemia induced H19 and MALAT1 and decreased GAS5 expression levels. Moreover, metformin decreased H19 and increased GAS5 expression in high glucose-treated cells. Case-control study findings revealed that the circulating levels of H19, MALAT1, and MEG3 were significantly elevated in T2D patients compared to the control subjects. Finally, results showed that the level of circulating H19 levels decreased while GAS5 increased in T2D patients after taking metformin for 2 months. CONCLUSION: The results of the current study provided evidence that metformin could exert its effect in the treatment of T2D by altering the expression levels of H19 and GAS5.

An updated review of the H19 lncRNA in human cancer: molecular mechanism and diagnostic and therapeutic importance.

Accumulating evidence has reported that H19 long non-coding RNA (lncRNA) expression level is deregulated in human cancer. It has been also demonstrated that de-regulated levels of H19 could affect cancer biology by various mechanisms including microRNA (miRNA) production (like miR-675), miRNA sponging and epigenetic modifications. Furthermore, lncRNA could act as a potential diagnosis and prognosis biomarkers and also a candidate therapeutic approach for different human cancers. In this narrative review, we shed light on the molecular mechanism of H19 in cancer development and pathogenesis. Moreover, we discussed the expression pattern and diagnostic and therapeutic importance of H19 as a potential biomarker in a range of human malignancies from breast to osteosarcoma cancer.