Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma

Huang, Shanzhou; Zhang, Chuanzhao; Sun, Chengjun; Hou, Ying; Zhang, Yixi; Tam, Nga Lei; Wang, Zekang; Yu, Jia; Huang, Bowen; Zhuang, Hongkai; Zhou, Zixuan; Ma, Zuyi; Sun, Zhonghai; He, Xiaoshun; Zhou, Qi; Hou, Baohua; Wu, Linwei

doi:10.18632/aging.102797

Cited by 28 publications

(37 citation statements)

References 44 publications

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“…Sun et al [7] indicated that OLA1 (DOC45) mRNA was overexpressed in cancers of the colon, rectum, stomach, ovary, uterus and lung, and the elevated expression of OLA1 protein was con rmed in colon cancer tissues. As consistent with our results, Huang et al [15] reported that OLA1 was highly expressed in hepatocellular carcinoma, and correlated with unfavorable clinical characteristics like tumor size, portal vein tumor thrombus and TNM stage, and predicted poor survival. Bai et al [9] found that OLA1 expression was signi cantly higher in lung cancer tissues than that in paired normal lung tissues.…”

Section: Discussionsupporting

confidence: 93%

“…With regard to the biological role of OLA1 in cancer cells, it is also still controversial. In hepatocellular carcinoma, downregulation of OLA1 signi cantly inhibited the proliferation, migration, invasion and tumorigenicity of hepatocellular carcinoma cells [15]. On the contrary, recent study on oral carcinoma revealed that knockdown OLA1 enhanced cell migrative ability, but have no effect on cell proliferation [10].…”

Section: Discussionmentioning

confidence: 97%

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The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

Wang

Zheng

Cao³

et al. 2021

Preprint

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Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 97%

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

Wang

Zheng

Cao³

et al. 2021

Preprint

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“…At the same time, the AUC value of the signature-based nomogram was nearly better than the AUC values of age, grade status and stage in 1-, 3, 5-years. Next, we further veri ed the mRNA expression of 6-genes (RBM45, PSMD1, OLA1, CCT6A , LCAT and IVD) for HCC patients in the Oncomine, TIMER, TCGA and ICGC database, which is consistent with the results of previous studies (18)(19)(20)(21). What's interesting, there are no reports of RBM45 and IVD genes in liver cancer.…”

Section: Discussionsupporting

confidence: 87%

Immune Prognostic Implications of PSMD14 and Its Associated Genes Signatures in Hepatocellular Carcinoma

Tian

Abudoureyimu

Lin

et al. 2020

Preprint

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BackgroundPSMD14 played a vital roles initiation and progression of hepatocellular carcinoma (HCC). However, PSMD14 and its-related genes for the immune prognostic implications of HCC patients have rarely been analyzed. Therefore, we aimed to explore gene signatures and immune prognostic values of PSMD14 and its-related genes in HCC.MethodsAnalyzed the expression of PSMD14 in multiple databases, and clinicopathologic characteristics associated with PSMD14 overall survival using Wilcoxon signed-ranktest, logistic and Cox regression, Kaplan-Meier method. An immune prognostic signature (including RBM45, PSMD1, OLA1, CCT6A, LCAT and IVD) was constructed and validated using the co-expression and cox regression analyses in TCGA, ICGC and TIMER datasets and CIBERSORT computational methods. Gene Set Enrichment Analysis (GSEA) was performed using TCGA data set. RT-PCR further validates the expression of seven immune genes in Hepatocellular carcinoma cells.ResultsIncreased PSMD14 expression in HCC was significantly associated with poor prognosis and clinicopathologic characteristics (grade, histologic stage, surgical approach and T stage, all p-values < 0.05 ). A total of six PSMD14-related genes were detected, which markedly related to overall survival and immune infiltrating levels in HCC patients. Using cox regression analysis, the PSMD14 and its-related genes were found to be an independent prognostic factor for HCC survival. Calibration curves confirmed good consistency between clinical nomogram prediction and actual observation. Immune prognostic model suggests that patients in the high‐risk group shown significantly poorer survival than patients in the low‐risk group.ConclusionWe screened potential immune prognostic genes and constructed and verified a novel PSMD14-based prognostic model of HCC, which provides new potential prognostic biomarkers and therapeutic targets and lays a theoretical foundation for immunotherapy of HCC.

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“…Upregulation of OLA1 is observed in various cancers, 63 and is associated with poor prognosis in breast and hepatocellular carcinomas 64,65 . Although OLA1 has ATPase or GTPase activity and contributes to stress responses in cells, 64,66 the precise role of OLA1 in carcinogenesis remains to be elucidated.…”

Section: Roles Of Brca1 In Centrosome Regulationmentioning

confidence: 99%

Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue‐specific carcinogenesis

Yoshino

Fang

et al. 2021

Cancer Science

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Alterations in breast cancer gene 1 (BRCA1), a tumor suppressor gene, increase the risk of breast and ovarian cancers. BRCA1 forms a heterodimer with BRCA1‐associated RING domain protein 1 (BARD1) and functions in multiple cellular processes, including DNA repair and centrosome regulation. BRCA1 acts as a tumor suppressor by promoting homologous recombination (HR) repair, and alterations in BRCA1 cause HR deficiency, not only in breast and ovarian tissues but also in other tissues. The molecular mechanisms underlying BRCA1 alteration‐induced carcinogenesis remain unclear. Centrosomes are the major microtubule‐organizing centers and function in bipolar spindle formation. The regulation of centrosome number is critical for chromosome segregation in mitosis, which maintains genomic stability. BRCA1/BARD1 function in centrosome regulation together with Obg‐like ATPase (OLA1) and receptor for activating protein C kinase 1 (RACK1). Cancer‐derived variants of BRCA1, BARD1, OLA1, and RACK1 do not interact, and aberrant expression of these proteins results in abnormal centrosome duplication in mammary‐derived cells, and rarely in other cell types. RACK1 is involved in centriole duplication in the S phase by promoting polo‐like kinase 1 activation by Aurora A, which is critical for centrosome duplication. Centriole number is higher in cells derived from mammary tissues compared with in those derived from other tissues, suggesting that tissue‐specific centrosome characterization may shed light on the tissue specificity of BRCA1‐associated carcinogenesis. Here, we explored the role of the BRCA1‐containing complex in centrosome regulation and the effect of its deficiency on tissue‐specific carcinogenesis.

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Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma

Cited by 28 publications

References 44 publications

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

Immune Prognostic Implications of PSMD14 and Its Associated Genes Signatures in Hepatocellular Carcinoma

Dysregulation of the centrosome induced by BRCA1 deficiency contributes to tissue‐specific carcinogenesis

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