miR-221 suppression through nanoparticle-based miRNA delivery system for hepatocellular carcinoma therapy and its diagnosis as a potential biomarker

Abstract

BackgroundMicroRNA-221(miR-221) is frequently dysregulated in cancer. The purpose of this study was to explore whether miR-221 can be used as a potential diagnostic marker or therapeutic target for hepatocellular carcinoma (HCC).MethodsIn this study, we investigated whether miR-221 expression was associated with clini-copathological characteristics and prognosis in HCC patients, and we developed a nanoparticle-based miRNA delivery system and detected its therapeutic efficacy in vitro and in vivo.ResultsWe found that miR-221 was upregulated in HCC tissues, cell lines and blood of HCC patients. Upregulated miR-221 was associated with clinical TNM stage and tumor capsular infiltration, and showed poor prognosis, suggesting that its suppression could serve as an effective approach for hepatocellular carcinoma therapy. Treatment of HCC cells with nanoparticle/miR-221 inhibitor complexes suppressed their growth, colony formation ability, migration and invasion. In vivo, the growth of the tumors treated by the nanoparticle/miR-221 inhibitor complexes were significantly less than those treated by the nanoparticle/miRNA scramble complexes. In addition, circulating miR-221 may act as a potential tumor biomarker for early diagnosis of HCC, and combined serum miR-221 and AFP detection gave a better performance than individual detection in early diagnosis of HCC.ConclusionThese findings suggest that a nanoparticle-based miRNA delivery system could potentially serve as a safe and effective treatment and miR-221 could also be a potential diagnostic marker for HCC.

MicroRNA 221/222 cluster kicks out Timp-3 to inflame the liver

“…Given that miR-221/222 are increased in HCC the targeted inhibition of miR-221/222 by locked nucleic acid (LNA)-anti-miRNA paves the way to clinical applications [ 10 ]. Since RNA is a gene regulator that can be edited, it has the potential to be translated to the clinical practice.…”

Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

“…Overexpression of miR-221 in hepatocytes enhanced cell proliferation due to a rapid S-phase entry and supported liver regeneration [203]. High expression of miR-221 in HCC patients also correlates with a poor survival [197,204]. It has been shown that miR-221 can promote EMT [205] as well as HCC cell migration [206].…”

“…Hepatic stellate cells, in turn, can promote a pro-metastatic environment In HCC, miR-221 was also described in numerous studies to be a striking example of a highly potent oncogenic miRNA ( Figure 6). MiR-221 levels are enhanced in HCC tissues, HCC cell lines and in the serum of HCC patients [40,[197][198][199]. Therefore, likewise as in melanoma, miR-221 could also serve as a biomarker for the diagnosis of HCC [200].…”

MicroRNA-221: A Fine Tuner and Potential Biomarker of Chronic Liver Injury

“…Such a system was employed in a study by Li et al, who used nanoparticles with miR-221 mimic/inhibitor, both in vivo and in vitro, in order to track HCC development. Nanoparticle-based miR-221 inhibitors decrease cell proliferation, colony formation ability and tumor development, and result in lower serum levels of miR-221, thus representing a promising approach for HCC therapy [58]. Additionally, Cai et al demonstrated that a synergistic effect is achieved with the usage of a combination treatment regimen of nanoparticles containing anti-miR-221 and chemotherapeutic drugs, such as sorafenib [59].…”