scholarly journals USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma

2021 ◽  
Vol 12 (9) ◽  
Author(s):  
Chi Lv ◽  
Shengli Wang ◽  
Lin Lin ◽  
Chunyu Wang ◽  
Kai Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Delayed Diagnosis ◽  
Specific Inhibitor ◽  
High Rate ◽  
Tumor Bearing ◽  
Resistant Disease ◽  
Potential Biomarker ◽  
Vascular Mimicry

AbstractHepatocellular carcinoma (HCC) is the most common visceral neoplasms with its heterogeneity and high rate of recurrence. HCC is characterized to be delayed diagnosis and the development of resistant disease. However, the molecular mechanism for HCC pathogenesis and progression remains largely unknown. Here, we demonstrated that ubiquitin-specific protease14 (USP14) is highly expressed in HCC samples, and the higher expression of USP14 is positively correlated with poor prognosis. Interestingly, USP14 is involved in the maintenance of HIF1-α stability to activate HIF1-α-induced transactivation via its deubiquitinase activity. USP14 depletion or its specific inhibitor IU1 treatment decreased cell proliferation, invasion, migration, and Vascular Mimicry (VM) formation even under hypoxia conditions in HCC cell lines. Moreover, we provided the evidence to show that knockdown of USP14 or USP14 inhibitor (IU1) treatment inhibited tumor growth in tumor-bearing nude mice. Our findings suggest that USP14 maintains HIF1-α stability through its deubiquitination activity, providing a potential biomarker for the early diagnosis and therapy of HCC.

scholarly journals TDO2 Was Downregulated in Hepatocellular Carcinoma and Inhibited Cell Proliferation by Upregulating the Expression of p21 and p27

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chengpeng Yu ◽  
Dean Rao ◽  
He Zhu ◽  
Qiumeng Liu ◽  
Wenjie Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Clinical Outcomes ◽  
Poor Prognosis ◽  
Kynurenine Pathway ◽  
Potential Biomarker ◽  
In Vivo Flow Cytometry

Background. Tryptophan-2,3-dioxygenase (TDO2) converts tryptophan into kynurenine in the initial limiting step of the kynurenine pathway. During the past decade, the overexpression of TDO2 has been found in various human tumors. However, the role of TDO2 in hepatocellular carcinoma is controversial, and we sought to clarify it in this study. Methods. Western blot analysis and immunochemistry were used to detect the expression of TDO2 in human tissue specimens. The effect of TDO2 on cell proliferation in vitro was assessed using CCK8 and colony formation assays, and a xenograft mouse model was used to detect the effect of TDO2 on tumor growth in vivo. Flow cytometry was used to assess the cell cycle status. Results. Low TDO2 expression was found in HCC and was associated with poor prognosis and adverse clinical outcomes. Conversely, TDO2 could restrain the proliferation of HCC cells in vivo and in vitro. Furthermore, TDO2 upregulated the expression of p21 and p27, inducing cell-cycle arrest. Conclusions. The loss of TDO2 expression in HCC was correlated with a poor prognosis and adverse clinical outcomes. At the same time, TDO2 could restrain the growth of HCC in vivo and in vitro. The results indicate that TDO2 is a potential biomarker and therapeutic target for HCC.

Upregulation of SKA3 enhances cell proliferation and correlates with poor prognosis in hepatocellular carcinoma

2021 ◽  
Vol 45 (4) ◽  
Author(s):  
Jianxin Tang ◽  
Jing Liu ◽  
Jinjun Li ◽  
Ziming Liang ◽  
Kaining Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Poor Prognosis

scholarly journals Increased expression of PDIA3 and its association with cancer cell proliferation and poor prognosis in hepatocellular carcinoma

2016 ◽  
Vol 12 (6) ◽  
pp. 4896-4904 ◽  
Author(s):  
Hideyuki Takata ◽  
Mitsuhiro Kudo ◽  
Tetsushi Yamamoto ◽  
Junji Ueda ◽  
Kousuke Ishino ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Poor Prognosis ◽  
Cancer Cell Proliferation

scholarly journals Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting the PI3K–AKT Pathway and Activating the AMPK–ROS Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuan Wei ◽  
Juanjuan Shi ◽  
Qianhan Lin ◽  
Xiaoxue Ma ◽  
Yingxin Pang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cisplatin Resistance ◽  
Specific Inhibitor ◽  
Bioinformatic Analysis ◽  
Akt Pathway ◽  
Metabolic Enzyme ◽  
Cancer Tissue

Background: Ovarian cancer is the most lethal female genital malignancy. Although cisplatin is the first-line chemotherapy to treat ovarian cancer patients along with debulking surgeries, its efficacy is limited due to the high incidence of cisplatin resistance. ATP citrate lyase (ACLY) has been shown to be a key metabolic enzyme and is associated with poor prognosis in various cancers, including ovarian cancer. Nevertheless, no studies have probed the mechanistic relationship between ACLY and cisplatin resistance.Methods: Survival analysis was mainly carried out online. Bioinformatic analysis was performed in R/R studio. Proliferative activity was measured by MTT and colony formation assays. Cell cycle and apoptosis analysis were performed by flow cytometry. The acquired-cisplatin-resistant cell line A2780/CDDP was generated by exposing A2780 to cisplatin at gradually elevated concentrations. MTT assay was used to calculate IC50 values of cisplatin. A xenograft tumor assay was used test cell proliferation in vivo.Results: Higher expression of ACLY was found in ovarian cancer tissue and related to poor prognosis. Knockdown of ACLY in A2780, SKOV3, and HEY cells inhibited cell proliferation, caused cell-cycle arrest by modulating the P16–CDK4–CCND1 pathway, and induced apoptosis probably by inhibiting p-AKT activity. Bioinformatic analysis of the GSE15709 dataset revealed upregulation of ACLY and activation of PI3K–AKT pathway in cells with acquired cisplatin resistance, in line with observations on A2780/CDDP cells that we generated. Knockdown of ACLY alleviated cisplatin resistance, and works synergistically with cisplatin treatment to induce apoptosis in A2780/CDDP cells by inhibiting the PI3K–AKT pathway and activating AMPK–ROS pathway. The ACLY-specific inhibitor SB-204990 showed the same effect. In A2780/CDDP cells, AKT overexpression could attenuate cisplatin re-sensitization caused by ACLY knockdown.Conclusions: Knockdown of ACLY attenuated cisplatin resistance by inhibiting the PI3K–AKT pathway and activating the AMPK–ROS pathway. These findings suggest that a combination of ACLY inhibition and cisplatin might be an effective strategy for overcoming cisplatin resistance in ovarian cancer.

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