The Similar Effects of miR-512-3p and miR-519a-2-5p on the Promotion of Hepatocellular Carcinoma: Different Tunes Sung With Equal Skill

Abstract

Although the therapeutic methods of hepatocellular carcinoma (HCC) have made great advances, the current situation is that HCC is the common malignancy. Our previous bioinformatic study presented that two members of C19MC (mir-512-1 and mir-519a-2) acted as crucial roles in the HCC progression. In this study, we first demonstrated that the miR-512-3p and miR-519a-2-5p, which were spliced from the mir-512-1 and mir-519a-2, were the functional mature miRNAs. Meanwhile, both miR-512-3p and miR-519a-2-5p were significantly upregulated in human HCC samples and HCC cell lines. The miR-512-3p and miR-519a-2-5p promoted the proliferation, invasion, and metastasis in vitro and in vivo. Moreover, the two miRNAs co-targeted the downstream tumor suppressors MAP3K2 and MAP2K4 and subsequently achieved the HCC progression. In the clinical cohort, high expression of miR-512-3p and miR-519a-2-5p acted as two risk factors for HCC recurrence and distinguished patients with poor tumor-free survival after radical resection. The integration of the two miRNAs into the AJCC staging system significantly improved the accuracy for the prediction of HCC recurrence. Our study suggests that miR-512-3p and miR-519a-2-5p have similar effects on the promotion of HCC progression. They can be robust markers for the prediction of HCC recurrence and therapy targets.

MiR-519a/522-5p from pancreatic cancer-secreted exosomes promotes tumor invasion by enhancing Warburg effect

“…Although the oncogenic effect of miR-519a/522-5p has been proved in multiple cancer types, the molecular mechanism is still largely unknown. We previously demonstrated that the members of C19MC including miR-519a and miR-512 could co-target the downstream MAPK pathway and promote invasion in HCC [31,32]. Tu et al [27] found that miR-519a promoted colony formation, proliferation and cell cycle progression in HCC cell lines by targeting PTEN/PI3K/AKT signaling.…”

Mir-4728 is a Valuable Biomarker for Diagnostic and Prognostic Assessment of HER2-Positive Breast Cancer

“…As described previously ( Rui et al, 2020b ), the total proteins extracted from the MFC-7 and ZR-75-1 were quantified and boiled. Then, the total proteins were electrophoresed with 10% SDS-PAGE gel (FD341-100, Fudebio, China) and transferred onto equilibrated polyvinylidene-difluoride membranes.…”

miRNAs in Liver Cancer

“…miRNA-512 may play one of the crucial roles in HCC progression, being significantly upregulated in human HCC samples and HCC cell lines. Along with miRNA-519, it targets tumor suppressors MAP3K2 and MAP2K4, and the integration of these two miRNAs into the AJCC staging system significantly improved the accuracy of the prediction of HCC recurrence [100]. Some of these miRNAs, such as miRNA-518b, miRNA-549, miRNA-2277, and miRNA-2355, are rarely mentioned in the context of liver cancer development, and their role in this process is yet to be elucidated.…”