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Background  Hepatocellular carcinoma (HCC) remains a major public health problem worldwide. The identification of effective chemotherapeutic targets for advanced HCC patients is urgently required. In this study, we investigated the role of protein phosphatase 2A-B55δ subunit (PP2A-B55δ, encoded by the  PPP2R2D  gene) and related mechanisms affecting chemotherapy sensitivity of HCC.    Methods  Experimental approaches for measuring the levels of  PPP2R2D  mRNA and B55δ protein in HCC included bioinformatics analyses, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting (WB), immunofluorescence and immunohistochemistry assays. Cell cycle, migration, colony formation, apoptosis, and cell proliferation assays in stable  PPP2R2D -knockdown and -overexpression cell lines  in vitro , and tumorigenicity assays  in vivo , were performed to explore the function of B55δ in cisplatin (cDDP) chemotherapy of HCC. Bioinformatics prediction, luciferase reporter assays, qRT-PCR, WB, and cell cycle analyses were used to reveal the regulatory relationship between microRNA-133b (miR-133b) and  PPP2R2D  expression. miR-133b mimic and inhibitor were used to elucidate the regulatory mechanism.    Results  Our studies showed that  PPP2R2D  expression was down-regulated in both HCC tumors and HCC cell lines. Treatment with cDDP increased the amount of B55δ protein. Artificially increasing the expression of B55δ counteracted cyclin-dependent kinase 1 activation, modulated transitions of the cell cycle, and increased the suppressive effect of cDDP on cell migration, colony formation, apoptosis, and proliferation  in vitro  and tumor growth  in vivo , thus enhancing therapeutic efficiency. In contrast, knockdown of B55δ partially inhibited the effect of cDDP chemotherapy. miR-133b was shown to regulate  PPP2R2D  expression by binding to the 3’-untranslated region of  PPP2R2D  mRNA. The miR-133b/ PPP2R2D  signaling pathway affects the effectiveness of cDDP chemotherapy.    Conclusions  PP2A-B55δ, regulated by miR-133b, enhances the sensitivity of HCC to cDDP chemotherapy. Our data indicate that PP2A-B55δ might be a novel and attractive target for increasing chemotherapy sensitivity of HCC.    Electronic supplementary material  The online version of this article (doi:10.1186/s13046-016-0341-z) contains supplementary material, which is available to authorized users.

Protein phosphatase 2A-B55δ enhances chemotherapy sensitivity of human hepatocellular carcinoma under the regulation of microRNA-133b