Adipose tissue-secreted miR-27a promotes liver cancer by targeting FOXO1 in obese individuals

Abstract

The current notion that obesity is a major risk factor for the development of and the mortality associated with a subset of liver cancer is well appreciated. However, detailed mechanistic insights underlying this relationship are lacking. Better understanding of the adipose tissue-secreted miRNAs that play a potential role in defining primary liver cancer development and mediating the obesity-cancer communication offers the potential for new insights into tumor growth and interventions to modulate tumor formation and progression. In this study, we clearly demonstrated that miR-27a is more highly upregulated in cancer, plasma, and adipose samples from obese liver cancer cases, and therefore reasoned that miR-27a excreted from adipose tissue leads to liver cancer development. To address this idea, we prepared miR-27a-overexpressing 3T3-L1 adipocytes and cocultured them with HepG2 liver cancer cells. Our results demonstrated that secretory miR-27a promoted liver cancer cell proliferation through the downregulation of the transcription factor FOXO1 and promoted the G1/S cell cycle transition by decreasing the cell cycle inhibitors p21 and p27 and increasing the cell cycle regulator cyclin D1. These findings improve our understanding of the involvement of miR-27a in obesity-liver cancer communication and might provide a novel putative target for obesity-driven primary liver cancer diagnosis and therapy.

Leucine promotes porcine myofibre type transformation from fast-twitch to slow-twitch through the protein kinase B (Akt)/forkhead box 1 signalling pathway and microRNA-27a

“…miRNA negatively regulate gene expression at the post-transcriptional level via binding to the 3′-untranslated region of target mRNA. Although human FoxO1 and mouse FoxO1 are targeted by miR-27a (39,40) , there is no evidence that porcine FoxO1 is a target of miR-27a, as leucine (4 mM) down-regulated both the expression of miR-27a and the protein expression of FoxO1 in this study.…”

Circulating Exosomal miR-27a and miR-130a Act as Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer

“…First, the sample size included was relatively small. Second, Karolina and colleagues reported that there was an association of miR-27a and patients with metabolic syndrome (37), and Sun and colleagues reported that adipose tissue could secreted miR-27a to promote liver cancer by targeting FOXO1 (38), which means miR-27a is significantly associated with metabolic diseases and cancers. Although there was no patients with colorectal cancer with metabolic syndrome or patients with type 2 diabetes enrolled in our study, further studies with a large number of subjects ought to consider these cofounding factors.…”

The mirn23a microRNA cluster antagonizes B cell development

“…Ikzf1 can induce FoxO1, which activates Ebf1 and Pax5 transcription, leading to sustained commitment to the B cell lineage [49,50]. Additionally, FoxO1 has been shown to be a direct target of miR-27a in several nonhematopoietic cell types [51][52][53][54][55]. We examined expression of Ikzf1 in Lin 2 progenitor cultures and observed that loss of mirn23a results in an ;1.75-fold overexpression of Ikzf1 (Fig.…”