Knockdown of SNHG3 or BMI1 and overexpression of miR-139-5p could inhibit cell proliferation, migration, and invasion in HCC. miR-139-5p was a target of SNHG3 and BMI1 was a direct target mRNA of miR-139-5p.
Here, we synthesized a panel of novel BMI1 inhibitors and examined their ability to alter cellular growth and eliminate cancer progenitor/stem-like cells in HCC with different p53 backgrounds.
Proliferation and colony formation of hepatoma cells were enhanced by treatment with HBV and LPS and were impaired by the suppression of Bmi1 and Dkk1 by small interfering RNAs.
We found that uc.338 promotes HCC cell proliferation and induces cell cycle progression through association with BMI1. uc.338 also modulated the transcription of CDKN1A.
The mRNA levels of EZH2 and Bmi-1 in HCC tissues and in Hep3B cells were significantly higher compared with those in normal samples (P < 0.01), while miR-203 level was significantly lower in HCC tissues (P < 0.01).
Our findings verify Bmi1 as a qualified treatment target for hepatocellular carcinoma (HCC) and support Bmi1 targeting treatment with chemotherapeutic agents.
The Bmi1 gene was silenced by Bmi1-siRNA (small interfering RNA) in the human HCC cell lines HepG2 and Bel-7402, and the gene expression levels were assayed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting.
The expression of Bmi1 and EZH2 was heterogeneous and associated with vascular infiltration, the histological grades, and the cell proliferation activity in HCC and HC-CC.