microRNA‑34a overexpression inhibits cell migration and invasion via regulating SIRT1 in hepatocellular carcinoma

Abstract

Abstract. Hepatocellular carcinoma (HCC) remains one of the most common types of malignancy with high mortality and morbidity rates. Previous studies have suggested that microRNAs (miRs) serve pivotal functions in various types of tumor. The aim of the present study was to assess the association between miR-34a expression and HCC cell migration and invasion, and the potential underlying mechanisms. The miR-34a overexpression vector or scramble control was transfected into human Hep3B and Huh7 cell lines. Transwell assays, and Matrigel and wound healing assays were used to detect the effects of miR-34a expression on HCC cell invasion and migration, respectively. The expression of miR-34a and the mRNA expression of other associated proteins were detected using quantitative reverse transcription polymerase chain reaction, and protein levels were measured using western blot analysis. Compared with the control, miR-34a expression was significantly downregulated in Hep3B and Huh7 cells, but this was reversed by the transfection with exogenous miR-34a (P<0.01). The number of migrated or invaded cells was significantly reduced by the overexpression of miR-34a in Hep3B or Huh7 cells (P<0.01). The expression of sirtuin 1 was upregulated, while the level of acetylate-p53 was downregulated by overexpression of miR-34a. Taken together, the results of the present study suggested that the overexpression of miR-34a may have suppressed HCC metastasis via inhibited cell migration and invasion.

Mir-34a-5p Mediates Cross-Talk between M2 Muscarinic Receptors and Notch-1/EGFR Pathways in U87MG Glioblastoma Cells: Implication in Cell Proliferation

“…Among these, mir-34a-5p was reported to be expressed at higher levels in wild type p53 than in the mutant GBM [ 22 ]. Furthermore, Notch-1 has already been validated as a miR-34a-5p target gene in several tumor histotypes [ 23 ] such as choriocarcinoma [ 24 ], breast cancer [ 25 ], and hepatocellular carcinoma [ 26 ]. We initially evaluated the levels of miR-34a-5p in both cell lines and in the normal brain.…”

“…In particular, in the wild-type p53-expressing U87MG cell line, a relevant role is played by mir-34a-5p ( Figure 8 A). According to the tumor-suppressive role of this microRNA in different tumor histotypes [ 24 , 25 , 26 , 27 ], we found that its expression is strongly downregulated in GBM cell lines in comparison to the normal human brain ( Figure 2 ). Interestingly the Notch expression appears directly correlated to mir-34a-5p expression; in fact the normal human brain, where the expression of mir-34a-5p is upregulated, the Notch-1 expression appears strongly reduced ( Figure 2 B).…”

<p>SIRT1 inhibits hepatocellular carcinoma metastasis by promoting M1 macrophage polarization via NF-&kappa;B pathway</p>

“…The tumorigenic influence of SIRT1 has been demonstrated in HCC in recent years, except for its influence on different biological reactions, such as inhibition of cell death and enhancement of proliferation, tumor stimulation, progression, and metastasis 23,24. It was verified that SIRT1 had an impact on tumorigenesis, metastasis, and clinical outcomes as well as resistance to chemotherapy in HCC, caused by deacetylation of tumor suppressor or oncogenic factors 25,26. Nevertheless, the role of SIRT1 in the regulation of M1-like macrophages and in HCC is unclear.…”

miR-34a Inhibits Cell Proliferation by Targeting SATB2 in Hepatocellular Carcinoma

“…Increasing researches have indicated that many miRNAs, including miR-34a [6], miR-211 [7], and miR-873 [8], are aberrantly expressed in HCC samples and exerted an effect in cell proliferation, apoptosis, and metastasis through regulating target mRNAs gene. Previous studies have shown that the miR-34a could affect the proliferation and apoptosis of hepatocellular carcinoma by regulating HDAC1 [9], c-Met [6], and SIRT1 [10]. At present, only Jiang G et al reported the expression level of SATB2 in hepatocellular carcinoma [7].…”