Transcriptional response profiles of paired tumor-normal samples offer novel perspectives in pan-cancer analysis

Hu, Shuofeng; Yuan, Hanyu; Li, Zongcheng; Zhang, Jian; Wu, Jiaqi; Chen, Yaowen; Shi, Qiang; Ren, Wu; Shao, Ningsheng; Ying, Xiaomin

doi:10.18632/oncotarget.17295

Cited by 28 publications

(26 citation statements)

References 53 publications

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“…Previous studies demonstrated that FAM64A contributes to cell cycle progression [ 43 , 44 , 45 ]. Overexpression of FAM64A was reported in leukemia, lymphoma and several types of solid cancer [ 46 ]. In breast cancer, overexpression of FAM64A enhanced the transactivation of NF-κB by disrupting the NF-κB/IκBα negative feedback loop [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Mizuno

Tanigawa

Nohata

et al. 2020

Cells

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Lung adenocarcinoma (LUAD) is the most aggressive cancer and the prognosis of these patients is unfavorable. We revealed that the expression levels of both strands of miR-99a (miR-99a-5p and miR-99a-3p) were significantly suppressed in several cancer tissues. Analyses of large The Cancer Genome Atlas (TCGA) datasets showed that reduced miR-99a-5p or miR-99a-3p expression is associated with worse prognoses in LUAD patients (disease-free survival (DFS): p = 0.1264 and 0.0316; overall survival (OS): p = 0.0176 and 0.0756, respectively). Ectopic expression of these miRNAs attenuated LUAD cell proliferation, suggesting their tumor-suppressive roles. Our in silico analysis revealed 23 putative target genes of pre-miR-99a in LUAD cells. Among these targets, high expressions of 19 genes were associated with worse prognoses in LUAD patients (OS: p < 0.05). Notably, FAM64A was regulated by both miR-99a-5p and miR-99a-3p in LUAD cells, and its aberrant expression was significantly associated with poor prognosis in LUAD patients (OS: p = 0.0175; DFS: p = 0.0276). FAM64A knockdown using siRNAs suggested that elevated FAM64A expression contributes to cancer progression. Aberrant FAM64A expression was detected in LUAD tissues by immunostaining. Taken together, our miRNA-based analysis might be effective for identifying prognostic and therapeutic molecules in LUAD.

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Section: Discussionmentioning

confidence: 99%

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

Mizuno

Tanigawa

Nohata

et al. 2020

Cells

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“…Previously, it was shown that FAM64A is up-regulated in various tumor cells and is involved in regulation of cell proliferation, while knockdown of FAM64A inhibits growth of cancer cells in vitro (18,21). In addition, FAM64A is significantly up-regulated in various types of tumor tissues, and high expression of FAM64A is associated with poor survival and clinical outcome, suggesting that FAM64A may be oncogenic in diverse types of cancers and it could be a potential prognostic marker and therapeutic target for cancer (40). In summary, our findings have identified a previously unreported function of FAM64A in the regulation of STAT3 activity, Th17 differentiation, colitis, and CAC development and have provided a potential therapeutic target for inflammatory disease and cancer.…”

Section: Discussionmentioning

confidence: 99%

FAM64A positively regulates STAT3 activity to promote Th17 differentiation and colitis-associated carcinogenesis

Zhang

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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STAT3 is a transcription factor that plays central roles in various physiological processes, including differentiation of Th cells. Its deregulation results in serious diseases, including inflammatory diseases and cancer. The mechanisms related to how STAT3 activity is regulated remain enigmatic. Here we show that overexpression of FAM64A potentiates IL-6-induced activation of STAT3 and expression of downstream target genes, whereas deficiency of FAM64A has the opposite effects. FAM64A interacts with STAT3 in the nucleus and regulates binding of STAT3 to the promoters of its target genes. Deficiency of Fam64a significantly impairs differentiation of Th17 but not Th1 or induced regulatory T cells (iTreg). In addition, Fam64a deficiency attenuates experimental autoimmune encephalomyelitis (EAE) and dextran sulfate sodium (DSS)-induced colitis, which is correlated with decreased differentiation of Th17 cells and production of proinflammatory cytokines. Furthermore, Fam64a deficiency suppresses azoxymethane (AOM)/DSS-induced colitis-associated cancer (CAC) in mice. These findings suggest that FAM64A regulates Th17 differentiation and colitis and inflammation-associated cancer by modulating transcriptional activity of STAT3.

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“…In a previous pan-cancer transcriptome study, KIF4A was also found to be upregulated in multiple cancer types, while STIL was not identi ed, probably due to the different p-values and fold-change thresholds applied in screening [26].…”

Section: Kif4a and Stil Overexpression Can Serve As Diagnostic And Prmentioning

confidence: 92%

“…Maternal embryonic leucine zipper kinase (MELK) has previously been identi ed, together with KIF4A, to be associated with poor prognosis in obese luminal A breast cancer patients [48]. Moreover, it was identi ed in another study as the top gene associated with elevated pan-cancer expression compared with normal tissue [26]. Pathway-enrichment analysis using GO was conducted on all ten hub genes based on GeneMANIA network analysis (Fig.…”

Section: Kif4a and Stil Coexpression And Interaction In Various Cancersmentioning

confidence: 99%

KIF4A and STIL act as pan-cancer diagnostic and prognostic biomarkers by bioinformatics analysis and verifcation in osteosarcoma

Pan

Luo

Lei

et al. 2020

Preprint

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Background: Cancer is a disease of abnormal cell proliferation that is caused by aberrantly expressed cancer-related genes. Transcriptome analysis to identify differential gene expression between tumors and paring normal tissue can help to reveal the key process of cell proliferation in cancer. Methods: By screening RNA-seq data covering twelve types of cancer and their paring normal tissue from the cancer genome atlas (TCGA), we identified twenty-eight cell-cycle-related genes that were overexpressed in no less than ten types of cancers. Results: Among them, kinesin family member 4A (KIF4A) and stromal tumor infiltrating lymphocyte (STIL) exhibited upregulated expression in eleven types of cancer, making them promising pan-cancer diagnostic markers. The high expression of either KIF4A or STIL indicates poor prognosis in four types of cancer. We further conducted the expression of KIF4A and STIL by immunohistochemistry（IHC） in osteosarcoma（OS） and paring normal tissue samples from a cohort of 57 osteosarcoma patients,which confirmed the results of bioinformatics analysis . Conclusions: KIF4A and STIL can serve as pan-cancer diagnostic and prognostic markers. The fact that they both function in the mitotic chromosome segregation process further emphasizes the importance of mitosis regulation and chromosome stability in carcinogenesis and cancer development.

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Transcriptional response profiles of paired tumor-normal samples offer novel perspectives in pan-cancer analysis

Cited by 28 publications

References 53 publications

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

FAM64A: A Novel Oncogenic Target of Lung Adenocarcinoma Regulated by Both Strands of miR-99a (miR-99a-5p and miR-99a-3p)

FAM64A positively regulates STAT3 activity to promote Th17 differentiation and colitis-associated carcinogenesis

KIF4A and STIL act as pan-cancer diagnostic and prognostic biomarkers by bioinformatics analysis and verifcation in osteosarcoma

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