The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

Wang, Dongmiao; Zhu, Yuming; Wang, Yanling; Li, Zhongwu; Yuan, Chunping; Zhang, Wei; Yuan, Hua; Ye, Jinhai; Yang, Jianrong; Jiang, Hongbing; Cheng, Jie

doi:10.1186/s12935-015-0252-7

Cited by 16 publications

(18 citation statements)

References 34 publications

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“…There have been several previous publications describing the association of LIN28B-usually in primary tumors-with adverse outcomes in other cancer types, including hepatocellular carcinoma 42 , oral squamous cell carcinoma 43 , breast cancer 44 , acute myeloid leukemia 45 , and multiple myeloma 46 . In addition, there seems to be a fundamental role of LIN28B in promoting the pathogenesis of MYCN-driven subsets of neuroblastoma 47 .…”

Section: Discussionmentioning

confidence: 99%

Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) lethality is due to metastatic dissemination. Characterization of rare, heterogeneous circulating tumor cells (CTCs) can provide insight into metastasis and guide development of novel therapies. Using the CTC-iChip to purify CTCs from PDAC patients for RNA-seq characterization, we identify three major correlated gene sets, with stemness genes LIN28B/KLF4, WNT5A, and LGALS3 enriched in each correlated gene set; only LIN28B CTC expression was prognostic. CRISPR knockout of LIN28Ban oncofetal RNA-binding protein exerting diverse effects via negative regulation of let-7 miRNAs and other RNA targets-in cell and animal models confers a less aggressive/ metastatic phenotype. This correlates with de-repression of let-7 miRNAs and is mimicked by silencing of downstream let-7 target HMGA2 or chemical inhibition of LIN28B/let-7 binding. Molecular characterization of CTCs provides a unique opportunity to correlated gene set metastatic profiles, identify drivers of dissemination, and develop therapies targeting the "seeds" of metastasis.

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Section: Discussionmentioning

confidence: 99%

Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target

et al. 2020

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“…Therefore, the total score ranged from 0 to 12. Accordingly, the immunoreactivity of each slide was categorized into three subgroups based on the final score: 0, negative; 1–4, low expression; 4–12, high expression, similar as our previous reports [ 8 , 15 , 16 ].…”

Section: Methodsmentioning

confidence: 98%

“…Negative controls (without primary antibody incubation) were included in each staining run. Immunoreactivity was semi-quantitatively evaluated according to staining intensity and distribution using the immunoreactive score which was calculated as intensity score × proportion score as we reported previously [ 8 , 15 , 16 ]. Intensity score was defined as 0, negative; 1, weak; 2, moderate; 3, strong.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma

Wang

et al. 2017

Cancer Cell Int

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ObjectiveIncreased expression of suppressor of zest 12 (SUZ12), a core component of the polycomb repressive complex 2, contributes to human tumorigenesis and associates with patient prognosis. In the present study, we sought to investigate the expression of SUZ12 and its clinicopathological significance in primary tongue squamous cell carcinoma (TSCC).MethodsThe expression of SUZ12 protein was determined by immunohistochemistry in clinical samples from a retrospective cohort of 72 patients with primary TSCC who were treated at our institution from Jan. 2007 to Dec. 2013. The potential associations between SUZ12 abundance and multiple clinicopathological parameters were assessed by Chi square test. Moreover, the effect of SUZ12 expression on patients’ survival was further estimated by Kaplan–Meier and Cox regression analyses.ResultsOur immunohistochemical staining data revealed aberrant overexpression of SUZ12 in a large subset of TSCC as compared to normal tongue mucosa. Elevated SUZ12 was found to be significantly associated with cervical nodes metastasis (P = 0.0325) and reduced overall as well as disease-free survival (Log-rank test, P = 0.0225, 0.0179, respectively). Both univariate and multivariate Cox regression analysis identified the expression status of SUZ12 (low/high) as an important independent prognostic factor for patients’ survival.ConclusionsOur data reveal that aberrant SUZ12 overexpression is associated with cervical nodes metastasis and reduced survival in TSCC. These findings suggest that SUZ12 might play critical roles during tongue tumorigenesis and serve as a novel biomarker with diagnostic and prognostic significance.

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“…In PDAC patients, high LIN28B expression was significantly correlated with high levels of lymphatic metastasis, distant metastasis and a poor prognosis. In addition, patients with increased LIN28B had markedly reduced overall survival compared to those with low LIN28B in HCC [62] and oral squamous cell carcinoma (OSCC) [63]. Thus, LIN28B is highly expressed in CRC and plays an important role in its pathogenesis, indicating that it is suitable as a target gene for CRC prognosis.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of RNA-binding proteins in human colorectal cancer

et al. 2020

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Background: Although RNA-binding proteins play an essential role in a variety of different tumours, there are still limited efforts made to systematically analyse the role of RNA-binding proteins (RBPs) in the survival of colorectal cancer (CRC) patients. Methods: Analysis of CRC transcriptome data collected from the TCGA database was conducted, and RBPs were extracted from CRC. R software was applied to analyse the differentially expressed genes (DEGs) of RBPs. To identify related pathways and perform functional annotation of RBP DEGs, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out using the database for annotation, visualization and integrated discovery. Protein-protein interactions (PPIs) of these DEGs were analysed based on the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Based on the Cox regression analysis of the prognostic value of RBPs (from the PPI network) with survival time, the RBPs related to survival were identified, and a prognostic model was constructed. To verify the model, the data stored in the TCGA database were designated as the training set, while the chip data obtained from the GEO database were treated as the test set. Then, both survival analysis and ROC curve verification were conducted. Finally, the risk curves and nomograms of the two groups were generated to predict the survival period. Results: Among RBP DEGs, 314 genes were upregulated while 155 were downregulated, of which twelve RBPs (NOP14, MRPS23, MAK16, TDRD6, POP1, TDRD5, TDRD7, PPARGC1A, LIN28B, CELF4, LRRFIP2, MSI2) with prognostic value were obtained. Conclusions: The twelve identified genes may be promising predictors of CRC and play an essential role in the pathogenesis of CRC. However, further investigation of the underlying mechanism is needed.

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The pluripotency factor LIN28B is involved in oral carcinogenesis and associates with tumor aggressiveness and unfavorable prognosis

Cited by 16 publications

References 34 publications

Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target

Pancreatic circulating tumor cell profiling identifies LIN28B as a metastasis driver and drug target

Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma

Integrated analysis of RNA-binding proteins in human colorectal cancer

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