MicroRNA-26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B-MEG3 axis

Abstract

miR-26a is known to play an important oncosuppressive role in HCC. However, its regulatory role and relationship with other non-coding RNAs is less clear. In the present study, we report that the expression levels of miR-26a and long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) were frequently downregulated in HCC tissues compared to matched non-malignant tissues. In addition, the expression levels of miR-26a and MEG3 were negatively correlated with the tumor sizes and TNM clinical stage in HCC patients. Overexpression of miR-26a significantly reduced the capacity of proliferation, invasion and migration of HCC cells. Moreover, we demonstrated that DNA methyltransferase 3b (DNMT3B) was a direct target gene of miR-26a. Overexpression of miR-26a suppressed the expression level of DNMT3B. Inhibited expression of DNMT3B showed similar tumor suppressive effects induced by miR-26a upregulation, and resulted in the upregulation of MEG3. Furthermore, we found that the expression levels of DNMT3B were upregulated in the HCC tissues compared with non-malignant tissues, and it was inversely correlated with miR-26a and MEG3 in HCC tissues. Thus, these results provided a plausible link between the observed reduction of miR-26a and MEG3 in HCCs. Together, the present study added miR-26a/DNMT3B/MEG3 axis to the complex mechanisms of HCC development.

LncRNA DGCR5 promotes lung adenocarcinoma (LUAD) progression via inhibiting hsa‐mir‐22‐3p

“…LncRNA UCA1 can promote renal cell carcinoma proliferation via epigenetically repressing p21 expression and negatively regulating miR‐495 (Lu et al, ). For another, microRNA‐26a inhibits proliferation and metastasis of human hepatocellular carcinoma by regulating DNMT3B‐MEG3 axis (Li et al, ). In lung cancer, by regulating lncRNA nuclear enriched abundant transcript 1 (NEAT1), microRNA‐449a inhibits lung cancer cell growth (You et al, ).…”

miR‐26a inhibits proliferation and promotes apoptosis in porcine immature Sertoli cells by targeting the PAK2 gene

“…miR‐26a‐5p promoted chicken follicular theca cell proliferation and significantly up‐regulated the expression of the anti‐apoptotic BCL2 gene to inhibit apoptosis by targeting a trinucleotide repeat containing 6A gene (Kang et al, ). In addition, miR‐26a also participates in regulating proliferation, apoptosis, migration, autophagy and invasion in multiple types of cancer cells, including vascular smooth muscle cells (Tan, Yang, Liu, & Yan, ), hepatocellular carcinoma cells (Jin et al, ; Li, Ren, et al, ), oesophageal squamous cell carcinoma cells (Li, Liang, et al, ; Yang et al, ) and gastric cancer cells (Ding et al, ), by targeting different genes. In this study, miR‐26a overexpression arrested cells in G0/G1 phase, inhibited proliferation and promoted swine Sertoli cells apoptosis.…”

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

“…Another potent tumor-suppressive miRNA is the miR-26a, which is strongly downregulated in both melanoma [36,89,147,[167][168][169] and HCC [40,144,150,[170][171][172][173] (Figure 5). In melanoma, re-expression of miR-26a induced cell cycle arrest and increased apoptosis [167,174].…”

“…Therefore, miR-26a has the potential to become a further promising target for future therapeutic approaches. In HCC, re-expression of miR-26a inhibited proliferation, migration and invasion [170]. MiR-26a was shown to target DNA methyltransferase 3 beta (DNMT3B), which is frequently upregulated in HCC tissues [170].…”

“…In HCC, re-expression of miR-26a inhibited proliferation, migration and invasion [170]. MiR-26a was shown to target DNA methyltransferase 3 beta (DNMT3B), which is frequently upregulated in HCC tissues [170]. Zhao et al recently showed that miR-26a re-expression in HCC reduced cell proliferation both in vitro and in a xenograft model [150].…”