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Background: Dysregulated epithelial–mesenchymal transition (EMT) is involved in cervical cancer metastasis and is associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive. Methods: Here, we systematically investigated the expression patterns of histone acetylation genes and their correlations with EMT pathway in cervical cancer. The expression of histone acetyltransferase CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effect of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were determined by cell growth curve, EdU assay, flow cytometryand xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effect of CSRP2BP on the cellinvasion, metastasis of cervical cancer cells in vivo and in vitro. RNA-seq, Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter were further applied to research for the roles and molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and matastasis. Results: We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis both in vitro and in vivo, while knockdown of CSRP2BP obtained the opposite effect. In addition, CSRP2BP-promoted resistant to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, and cooperate with the transcription factor SMAD4, bound to the SEB2 domain of the N-cadherin gene promotor region and upregulated N-cadherin transcription. Consequently, CSRP2BP involved cervical cancer cell EMT and matastasis dependent on activating N-cadherin. Conclusions: These findings reveal for the first time the involvement of histone acetyltransferase CSRP2BP in cervical cancer metastasis partially through promoting the EMT process and imply that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis.

Background Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression and play fundamental roles in various types of cancer. Current developments in transcriptome analyses unveiled the existence of lncRNAs; however, their functional characterization remains a challenge. Methods A bioinformatics screen was performed by integration of multiple omics data in hepatocellular carcinoma (HCC) prioritizing a novel oncogenic lncRNA, LINC01132. Expression of LINC01132 in HCC and control tissues was validated by qRT-PCR. Cell viability and migration activity was examined by MTT and transwell assays. Finally, our results were confirmed in vivo mouse model and ex vivo patient derived tumor xenograft experiments to determine the mechanism of action and explore LINC01132-targeted immunotherapy. Results Systematic investigation of lncRNAs genome-wide expression patterns revealed LINC01132 as an oncogene in HCC. LINC01132 is significantly overexpressed in tumor and associated with poor overall survival of HCC patients, which is mainly driven by copy number amplification. Functionally, LINC01132 overexpression promoted cell growth, proliferation, invasion and metastasis in vitro and in vivo. Mechanistically, LINC01132 acts as an oncogenic driver by physically interacting with NRF and enhancing the expression of DPP4. Notably, LINC01132 silencing triggers CD8+ T cells infiltration, and LINC01132 knockdown combined with anti-PDL1 treatment improves antitumor immunity, which may prove a new combination therapy in HCC. Conclusions LINC01132 functions as an oncogenic driver that induces HCC development via the NRF1/DPP4 axis. Silencing LINC01132 may enhance the efficacy of anti-PDL1 immunotherapy in HCC patients.