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Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, which exerts anticancer effects in various cancers. However, the molecular mechanisms underlying the therapeutic effects of shikonin against endometrioid endometrial cancer (EEC) have not yet been fully elucidated. Herein, we investigated anticancer effects of shikonin on EEC cells and explored the underlying molecular mechanism. We observed that shikonin inhibits proliferation in human EEC cell lines in a dose-dependent manner. Moreover, shikonin-induced apoptosis was characterized by the up-regulation of the pro-apoptotic proteins cleaved-Caspase-3 and Bax, and the down-regulation of the anti-apoptotic protein Bcl-2. Microarray analyses demonstrated that shikonin induces many miRNAs’ dysregulation, and miR-106b was one of the miRNAs being most significantly down-regulated. miR-106b was identified to exert procancer effect in various cancers, but in EEC remains unclear. We first confirmed that miR-106b is up-regulated in EEC tissues and cells, and knockdown of miR-106b suppresses proliferation and promotes apoptosis. Meanwhile, our results validated that the restored expression of miR-106b abrogates the antiproliferative and pro-apoptotic effects of shikonin. We also identified that miR-106b targets phosphatase and tensin homolog (PTEN), a tumor suppressor gene, which in turn modulates AKT/mTOR signaling pathway. Our findings indicated that shikonin inhibits proliferation and promotes apoptosis in human EEC cells by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway, suggesting shikonin could act a potential therapeutic agent in the EEC treatment.

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We aim to investigate the expression and clinical significance of the tubulin gamma complex-associated protein 4 (TUBGCP4) in hepatocellular carcinoma (HCC). The mRNA expression of TUBGCP4 in HCC tissues was analyzed using The Cancer Genome Atlas (TCGA) database. Paired HCC and adjacent nontumor tissues were obtained from HCC patients to measure the protein expression of TUBGCP4 by immunohistochemistry (IHC) and to analyze the relationship between TUBGCP4 protein expression and the clinicopathological characteristics and the prognosis of HCC patients. We found that TUBGCP4 mRNA expression was upregulated in HCC tissues from TCGA database. IHC analysis showed that TUBGCP4 was positively expressed in 61.25% (49/80) of HCC tissues and 77.5% (62/80) of adjacent nontumor tissues. The Chi-square analysis indicated that the positive rate of TUBGCP4 expression between HCC tissues and the adjacent nontumor tissues was statistically different ( P < 0.05 ). Furthermore, we found that TUBGCP4 protein expression was correlated with carbohydrate antigen (CA-199) levels of HCC patients ( P < 0.05 ). Further, survival analysis showed that the overall survival time and tumor-free survival time in the TUBGCP4 positive group were significantly higher than those of the negative group ( P < 0.05 ), indicating that the positive expression of TUBGCP4 was related to a better prognosis of HCC patients. COX model showed that TUBGCP4 was an independent prognostic factor for HCC patients. Our study indicates that TUBGCP4 protein expression is downregulated in HCC tissues and has a relationship with the prognosis of HCC patients.