Dataset Information

2-(2-nitrobenzylidene) indolin-3-one compound inhibits transmembrane prostate androgen-induced protein (TMEPAI) expression and cancer cell proliferation.

ABSTRACT:

Objectives

The transmembrane prostate androgen-induced protein (TMEPAI) is aberrantly expressed in many cancer and plays a crucial role in tumourigenesis, which makes it a potential cancer therapeutic target for drug discovery.

Materials and methods

Here, we employed a firefly luciferase reporter driven by the TMEPAI gene promoter to screen for compound capable of inhibiting the expression of TMEPAI, and the effects of TMEPAI inhibitor on cancer cell proliferation were evaluated using the colony formation assay, cell cycle analysis, Ki-67 immunofluorescence assay and EdU incorporation assay.

Results

2-(2-nitrobenzylidene) indolin-3-one (JHY-A007-50) was identified and shown to effectively inhibit the TMEPAI promoter activity. Further studies revealed that JHY-A007-50 specifically inhibited the expression of TMEPAI at both the mRNA and protein levels. Moreover, we found that JHY-A007-50 could inhibit cell proliferation and induce cell cycle arrest at the G1 phase. Our results showed that overexpression of TMEPAI decreased the inhibitory effects of JHY-A007-50 on cancer cell proliferation, and JHY-A007-50 did not affect the cell viability of HeLa cells knocked down of TMEPAI.

Conclusions

Taken together, these results suggest that compound JHY-A007-50 mediates the downregulation of TMEPAI expression and inhibits cell proliferation in cancer cells.

SUBMITTER: Li Y

PROVIDER: S-EPMC6528943 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Sirtuin-7 (SIRT7) is associated with the maintenance of tumorigenesis. However, its functional roles and oncogenic mechanisms in prostate cancer (PCa) are poorly understood. Here, we investigated the roles and underlying molecular mechanisms of SIRT7 in PCa cell growth and androgen-induced autophagy. METHODS:The LNCap and 22Rv1 PCa cell lines were subjected to quantitative reverse transcription (RT)-PCR to characterize their genes encoding SIRT7, AR, and SMAD4. The proteins produced from these genes were quantified by western blotting and immunoprecipitation analysis. SIRT7-depleted cells were produced by transfection with plasmid vectors bearing short hairpin RNAs against SIRT7. The proliferation of each cell line was assessed by CCK8 and EdU assays. Autophagic flux was tracked by mRFP-GFP-LC3 adenovirus under an immunofluorescence microscope. Apoptosis was evaluated by flow cytometry. Tumors were induced in mouse axillae by injection of the cell lines into mice. Tumor morphology was examined by immunohistochemistry and relative tumor growth and metastases were compared by a bioluminescence-based in vivo imaging system. RESULTS:SIRT7 depletion significantly inhibited cell proliferation, androgen-induced autophagy, and invasion in LNCap and 22Rv1 cells (in vitro) and mouse xenograft tumors induced by injection of these cells (in vivo). SIRT7 knockdown also increased the sensitivity of PCa cells to radiation. Immunohistochemical analysis of 93 specimens and bioinformatic analysis revealed that SIRT7 expression was positively associated with androgen receptor (AR). Moreover, the AR signal pathway participated in SIRT7-mediated regulation of PCa cell proliferation, autophagy, and invasion. SIRT7 depletion downregulated the AR signal pathway by upregulating the level of SMAD4 protein in PCa cells. CONCLUSION:SIRT7 plays an important role in the development and progression of human PCa and may be a promising prognostic marker for prostate cancer.