Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Zhou, Jun; Hui, Xiao liang; Mao, Ying; Fan, Li ya

doi:10.1042/bsr20190625

Cited by 42 publications

(51 citation statements)

References 62 publications

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“…It was con rmed that the high expression of miR-744 was signi cantly related to lymph node metastasis and poor prognosis of NSCLC, and was an independent prognostic molecular marker of NSCLC. This is comparable to ndings in the studies on pancreatic cancer [19][20][21], prostate cancer [23,24] and nasopharyngeal carcinoma [4,36]. All of these suggested that miR-744 might play an important role in the process of NSCLC progression and metastasis, and need to be further studied.…”

Section: Discussionsupporting

confidence: 85%

MiR-744 facilitates non-small cell lung cancer progression by direct transcriptional regulation and indirect MAPK pathway activation mediated upregulation of C-FOS

Zhu

2020

Preprint

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Background: Metastasis is the leading cause of lung cancer associated death. Here, we focused on the function and molecular mechanism of miR-744 and its potential clinical application in lung carcinoma. Methods: The clinical cohort and data from TCGA were analyzed for the correlation of miR-744 and outcomes. Multiple NSCLC cell lines and a xenograft model were applied for the functional studies. Reporter assays were explored for transcriptional regulatory mechanism.Results: It was confirmed that the overexpression of miR-744 was significantly correlated with lymph node metastasis and poor prognosis in NSCLC. Both in vitro and in vivo studies revealed that miR-744 overexpression aggravated the growth, invasion and metastasis of NSCLC cells. MiR-744 enhanced the resistance of lung cancer cells to radiotherapy and paclitaxel. MiR-744 positively regulated C-FOS by directly binding to the promoter of C-FOS and -1195 to -1227 and -298 to -323 bp upstream of C-FOS gene were the direct and efficient miR-744 binding sites. MiR-744 could also indirectly upregulate c-FOS protein by activating MAPK pathway.Conclusion: Our findings uncover the function and a novel mechanism of miR-744 in mediating growth and metastasis of NSCLC cells. Our data suggests that miR-744 may serve as a possible therapeutic target for NSCLC.

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Section: Discussionsupporting

confidence: 85%

MiR-744 facilitates non-small cell lung cancer progression by direct transcriptional regulation and indirect MAPK pathway activation mediated upregulation of C-FOS

Zhu

2020

Preprint

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“…[14][15][16] High expression of miR-196a, miR-27a, miR-221, miR-143, miR-135b, miR-199b-5p and miR-21, but low expression of miR-744, miR-455-3p and miR-655, in pancreatic cancer samples were found compared with normal samples and associated with poor prognosis. 17 In addition, the expression profile of miRNAs varies even in the different locations, 18 which further confirms that miRNAs have high application value in the diagnosis, prognosis evaluation and treatment of pancreatic cancer. Recently, a widely reported miRNA, miR-939, has been pointed out to be pivotal in the development and procession of cancers, such as hepatocellular carcinoma, 19 tongue squamous cell carcinoma, 20 gastric, 21 lung, 22 colorectal, 23 and ovarian cancer.…”

Section: Introductionmentioning

confidence: 75%

<p>miR-939-5p Contributes to the Migration and Invasion of Pancreatic Cancer by Targeting ARHGAP4</p>

Shen¹,

Chen²,

Gao³

et al. 2020

OTT

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Rho GTPase-activating protein 4 (ARHGAP4) is a GTPase-activating protein for the small GTPases of the Rho family that is involved in tumorigenesis. We recently reported that ARHGAP4 can mediate Warburg effect and malignant phenotype of pancreatic cancer. However, the regulation of ARHGAP4 remains unclear. Methods: ARHGAP4 and miR-939-5p expressions in pancreatic cancer tissues and cell lines were measured by real-time PCR or Western blotting. Pancreatic cancer cells were transfected with miR-939-5p inhibitor, miR-939-5p mimic and/or lentivirus expressing ARHGAP4, and the cell viability, invasion and migration were measured by CCK-8 and Transwell assay, respectively. The suppression of ARHGAP4 expression by miR-939-5p was revealed by luciferase reporter assay, real-time PCR or Western blotting. Results: ARHGAP4 expression was decreased, while miR-939-5p was increased in pancreatic cancer tissues compared with adjacent-normal pancreatic tissues. Higher miR-939-5p expression was correlated with advanced pathological stages and poor prognosis of pancreatic cancer patients. miR-939-5p directly targeted ARHGAP4. Either miR-939-5p down-regulation or ARHGAP4 overexpression inhibited viability, invasion and migration of pancreatic cancer cells. However, ARHGAP4 overexpression markedly inhibited the increased viability, migration, and invasion induced by miR-939-5p up-regulation in pancreatic cancer cells. Conclusion: These observations suggested that miR-939-5p regulates the malignant phenotype of pancreatic cancer cells by targeting ARHGAP4, establishing miR-939-5p as a novel regulator of ARHGAP4 with a critical role in tumorigenesis in pancreatic cancer.

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“…Meanwhile, a large number of cancer-related data are stored in publicly available databases, such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). A reanalysis of these data could facilitate the discovery of a vast range of valuable biological information (Gao et al, 2018(Gao et al, , 2019Liu et al, 2019;Zhou et al, 2019). For instance, several novel genes associated with poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) were identified by analyzing the array data from GEO.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, several novel genes associated with poor prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) were identified by analyzing the array data from GEO. These genes might serve as potential diagnostic and prognostic biomarkers for PDAC (Zhou et al, 2019). Liu et al (2019) revealed a novel robust four-gene metabolic signature predicting overall survival for hepatocellular carcinoma (HCC) by mining mRNA expression profiles and clinicopathological data from TCGA and GSE14520 data sets.…”

Section: Introductionmentioning

confidence: 99%

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

Gao

Yang

2020

DNA and Cell Biology

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The aim of this study was to identify genes with clinical significance in colorectal cancer (CRC). Gene expression profiles of 585 CRC tissues and 61 normal colorectal tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to identify differentially expressed genes (DEGs) between CRC and normal colorectal tissues. DAVID and KOBAS tools were used to explore Gene Ontology (GO) and KEGG pathways enriched by DEGs, respectively. In addition, TCGA data sets were also used to identify prognostic factors and develop a prognostic prediction model for CRC. A total of 353 DEGs including 117 upregulated and 236 downregulated genes in CRC were identified based on GSE32323 data set. These DEGs were significantly enriched in the biological process related to the regulation of cell proliferation and 50 signaling pathways, such as ''TGF-beta signaling pathway,'' ''Wnt signaling pathway,'' and ''Jak-STAT signaling pathway.'' GCG, ADH1B, SLC4A4, ZG16, and CLCA4 were the top five downregulated in CRC. FOXQ1, LGR5, CLDN1, KRT23, and DPEP1 were the top five upregulated in CRC. KRT23 expression could affect tumor stage and regional lymph node metastasis in CRC patients. FOXQ1 expression could affect tumor distant metastasis in CRC patients. Survival analysis indicated that SLC4A4 expression was associated with the prognosis of CRC patients. Prognostic prediction model developed based on age, tumor stage, and SLC4A4 expression exhibited an efficient performance in predicting 1-, 3-, and 5-year overall survival of CRC patients. In conclusion, the current study identified several genes and pathways related to CRC, which provided new insight in understanding molecular mechanism of tumorigenesis and development of CRC.

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Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Cited by 42 publications

References 62 publications

MiR-744 facilitates non-small cell lung cancer progression by direct transcriptional regulation and indirect MAPK pathway activation mediated upregulation of C-FOS

MiR-744 facilitates non-small cell lung cancer progression by direct transcriptional regulation and indirect MAPK pathway activation mediated upregulation of C-FOS

<p>miR-939-5p Contributes to the Migration and Invasion of Pancreatic Cancer by Targeting ARHGAP4</p>

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

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