The Down-Regulation of SUZ12 Accelerates the Migration and Invasion of Liver Cancer Cells via Activating ERK1/2 Pathway

Xue, Cailin; Wang, Kunyuan; Jiang, Xiaofeng; Gu, Chengxin; Yu, Ganxiang; Zhong, Yun; Liu, Shiming; Nie, Yongzhan; Zhou, Yongjian; Yang, Hui

doi:10.7150/jca.29932

Cited by 25 publications

(15 citation statements)

References 40 publications

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“…It is a component of the PRC2/EED-EZH2 complex, which methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene [74]. Further, we observed different studies reported SUZ12 for the treatment of hepatocellular carcinoma [75,76]. We have also tried to investigate the therapeutic applications of the identified prognostic markers.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the upregulation of SUZ12 was reported to be a prognostic factor for poor prognosis of various malignancies [88,89]. But, in contrast, recently, one of the studies has shown that the lower expression of SUZ12 results in poor prognosis in terms of the 5-year survival of HCC patients [76]. Xue et al, further demonstrated the significant down-regulation of SUZ12 in HBV-related HCC tissue samples in comparison to normal samples; and its overexpression impaired HCC cell’s migration and invasion [76].…”

Section: Discussionmentioning

confidence: 99%

“…But, in contrast, recently, one of the studies has shown that the lower expression of SUZ12 results in poor prognosis in terms of the 5-year survival of HCC patients [76]. Xue et al, further demonstrated the significant down-regulation of SUZ12 in HBV-related HCC tissue samples in comparison to normal samples; and its overexpression impaired HCC cell’s migration and invasion [76]. Thus, more studies on HCC cohorts can confirm the exact role of SUZ12 in the prognosis of HCC patients.…”

Section: Discussionmentioning

confidence: 99%

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Integrative multi-omics approach for stratification of tumor recurrence risk groups of Hepatocellular Carcinoma patients

Kaur

Lathwal

Raghava

2021

Preprint

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Postoperative tumor recurrence is one of the major concerns associated with the poor prognosis of HCC patients. There is yet to elucidate a standard surveillance system for HCC recurrence risk owing to complexity of this malignancy. Generation of multi-omics data from patients facilitate the identification of robust signatures for various diseases. Thus, the current study is an attempt to develop the prognostic models employing multi-omics data to significantly (p-value <0.05) stratify the recurrence high-risk (median Recurrence Free Survival time (RFS) =<12 months) and low-risk groups (median RFS >12 months). First, we identified key 90RNA, 50miRNA and 50 methylation features and developed prognostic models; attained reasonable performance (C-Index >0.70, HR >2.5), on training and validation datasets. Subsequently, we developed a prognostic (PI) model by integrating the four multi-omics features (SUZ12, hsa-mir-3936, cg18465072, and cg22852503), that are biologically inter-linked with each other. This model achieved reasonable performance on training and validation dataset, i.e. C-Index 0.72, HR of 2.37 (1.61 - 3.50), p-value of 6.72E-06, Brier score 0.19 on training dataset, and C-Index 0.72 (95% CI: 0.63 - 0.80), HR of 2.37 (95% CI: 1.61 - 3.50), p-value of 0.015, Brier score 0.19 on validation dataset. Eventually, Drugbank data was investigated to elucidate therapeutic potential of these signatures. We have identified nine potential drugs against three genes (CA9, IL1A, KCNJ15) that are positively correlated with the tumor recurrence. We anticipate these results from our study will help researchers and clinicians to improve the HCC recurrence surveillance, eventually outcome of patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Integrative multi-omics approach for stratification of tumor recurrence risk groups of Hepatocellular Carcinoma patients

Kaur

Lathwal

Raghava

2021

Preprint

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“…PPI analysis revealed those seven miRNAs' target genes with the strongest protein interactions. Moreover, it has been reported that the abnormal expression of RNF2, AGO1, CREBBP, and SUZ12 is closely related to the invasion and metastasis of HCC [ 32 – 35 ]. These results indicate that MRMs are associated with metastasis of HCC.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma

Yuan

Wang

et al. 2021

Journal of Oncology

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Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. Abnormal expression of miRNAs is believed to play a role in the recurrent metastasis of HCC. However, limited studies on the role of miRNAs in HCC metastasis have been carried out. Therefore, this study is aimed at exploring the potential value of metastasis-related miRNAs (MRMs) in HCC. We retrieved MRMs were from the Human Cancer Metastasis Database. Differential miRNAs were identified for tumor samples of HCC patients and normal samples based on the TCGA database. Further, univariate and multivariate Cox regression analyses were used to screen MRMs known to be independent prognostic factors in HCC. These MRMs were then used to build a prognostic signature. All patients were classified into high-risk and low-risk groups based on the median of the signature scores. Moreover, GO and KEGG pathway enrichment analyses were performed to predict the function of these MRMs. Finally, a nomogram was constructed to predict the OS of patients at 1, 2, and 3 years. In our study, a total of seven prognostic MRMs (miR-140-3p, miR-9-5p, miR-942-5p, miR-324-3p, miR-29c-5p, miR-551a, and miR-149-5p) were identified and used for constructing the prognostic signature based on the training cohort. Patients in the low-risk HCC group showed better overall survival (OS) than those in the high-risk group. The results were validated using the validation cohort. In summary, the findings of this study provide evidence that MRMs-based prognostic signature is an independent biomarker in the prognosis of HCC patients.

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“…39,40 MMP2 and MMP9 are EMT markers that could be increased significantly during EMT process. 41,42 Therefore, changes in EMT-related gene expressions serve as important markers in indicating the degree of metastasis in tumor cells. In the present research, our results showed that miR-524-5p/FSTL1 could significantly regulate migration and invasion of BC cells.…”

Section: The Role Of Mir-524-5p In Breast Cancermentioning

confidence: 99%

MiR-524-5p Suppresses Migration, Invasion, and EMT Progression in Breast Cancer Cells Through TargetingFSTL1

Jin

Zhang

2020

Cancer Biotherapy and Radiopharmaceuticals

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Background: The effects of miR-524-5p on breast cancer (BC) have not been investigated, though studies show that miR-524-5p has an anticancer function. Thus, this study investigated the effects of miR-524-5p on BC cells and its potential molecular mechanism. Materials and Methods: The expression of miR-524-5p from the collected BC samples was determined. Cell counting kit-8 (CCK-8) assay was performed to examine the effect of miR-524-5p on BC cells viability. The target for miR-524-5p was predicted by bioinformatics and further verified by luciferase assay. Wound healing assay and transwell assay were performed to determine cell migration and invasion of BC cells. The expressions of Follistatin-like 1 (FSTL1) and related proteins in epithelial-mesenchymal transition (EMT) were detected by Western blotting and quantitative real-time polymerase chain reaction. Results: MiR-524-5p was low-expressed in BC samples, and upregulation of miR-524-5p suppressed BC cell viability, migration, and invasion. FSTL1 was predicted as a target for miR-524-5p. In addition, overexpressed FSTL1 effectively abolished the effect of miR-524-5p on inhibiting FSTL1 expression, and reversed the inhibitory effects of miR-524-5p on the migration, invasion of BC cells as well as the effect of miR-524-5p on regulating the expressions of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), E-cadherin, and N-cadherin. Conclusions: Our findings suggest that miR-524-5p targeting FSTL1 adversely affects the progression of migration, invasion, and EMT of BC cells, thus, miR-524-5p is possibly a target for BC treatment.

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The Down-Regulation of SUZ12 Accelerates the Migration and Invasion of Liver Cancer Cells via Activating ERK1/2 Pathway

Cited by 25 publications

References 40 publications

Integrative multi-omics approach for stratification of tumor recurrence risk groups of Hepatocellular Carcinoma patients

Integrative multi-omics approach for stratification of tumor recurrence risk groups of Hepatocellular Carcinoma patients

Identification of a Novel Metastasis-Related miRNAs-Based Signature for Predicting the Prognosis of Hepatocellular Carcinoma

MiR-524-5p Suppresses Migration, Invasion, and EMT Progression in Breast Cancer Cells Through TargetingFSTL1

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