Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5

Ando, Yuichi; Ohuchida, Kenoki; Otsubo, Yoshiki; Kibe, Shin; Takesue, Shin; Abe, Toshiya; Iwamoto, Chika; Shindo, Koji; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Ohtsuka, Takao; Oda, Yoshinao; Nakamura, Masafumi

doi:10.1371/journal.pone.0228015

Cited by 88 publications

(67 citation statements)

References 55 publications

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“…CENPF, for instance, has been related to worse outcomes and survival in several cancer types ( 80 , 81 ). Another outstanding example is the MLKL gene, which was shown to be up-regulated in pancreatic cancer, as we observed with Reboot, especially in tumor-invasion conditions ( 82 ). The transcription factor TFDP1 is a gene with significant somatic copy number alterations and corresponding somatic gene expression changes were observed in papillary thyroid carcinomas ( 83 ), even though whose functions remain uncovered in cancer.…”

Section: Discussionsupporting

confidence: 54%

Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis

et al. 2021

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Nowadays, the massive amount of data generated by modern sequencing technologies provides an unprecedented opportunity to find genes associated with cancer patient prognosis, connecting basic and translational research. However, treating high dimensionality of gene expression data and integrating it with clinical variables are major challenges to perform these analyses. Here, we present Reboot, an integrative approach to find and validate genes and transcripts (splicing isoforms) associated with cancer patient prognosis from high dimensional expression datasets. Reboot innovates by using a multivariate strategy with penalized Cox regression (LASSO method) combined with a bootstrap approach, in addition to statistical tests and plots to support the findings. Applying Reboot on data from 154 glioblastoma patients, we identified a three-gene signature (IKBIP, OSMR, PODNL1) whose increased derived risk score was significantly associated with worse patients’ prognosis. Similarly, Reboot was able to find a seven-splicing isoforms signature related to worse overall survival in 177 pancreatic adenocarcinoma patients with elevated risk scores after uni- and multivariate analyses. In summary, Reboot is an efficient, intuitive and straightforward way of finding genes or splicing isoforms signatures relevant to patient prognosis, which can democratize this kind of analysis and shed light on still under-investigated cancer-related genes and splicing isoforms.

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Section: Discussionsupporting

confidence: 54%

Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis

et al. 2021

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“…For example, elevated levels of CXCL5 were detected in human NSCLC that was related to the vascularity of these tumors [12]. Ando et al research showed that CXCL5 could promote pancreatic cell migration and invasion by mediating the necroptosis [13]. Recently, Liu et al reported that overexpression of CXCL5 dramatically attenuated the suppressive effects of cell proliferation, migration and invasion induced by ROR-α-1 overexpression in hepatocellular carcinoma [14].…”

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confidence: 99%

Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5

et al. 2020

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Background Long noncoding RNAs (LncRNAs) have been reported to critically regulate gastric cancer (GC). Recently, it was reported that LBX2 antisense RNA 1 (LBX2-AS1) is abnormally expressed in GC. However, the role of LBX2-AS1 in the malignancy of GC is worth further discussion. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the LBX2-AS1, miR-4766-5p and C-X-C motif chemokine (CXCL5) expression in GC tissues and cells. Dual-luciferase reporter assay was applied to examine the target relationship between LBX2-AS1 and miR-4766-5p or miR-4766-5p and CXCL5. Cell counting kit-8 (CCK-8) and Transwell assays were used to detect cell proliferation, migration and invasion rates. The protein expression of CXCL5 was confirmed using western blot. The RNA pull down experiment was used to verify the specificity of LBX2-AS1 and miR-4766-5p on BGC-823 and SGC-7901 cells. Results LBX2-AS1 was up-regulated in GC tissues and cells, and its knockdown suppressed proliferation, migration and invasion of GC cells. While, overexpression of LBX2-AS1 increased proliferation and increased CXCL5 mRNA level. CXCL5 improved cell proliferation, migration and invasion of GC cells. LBX2-AS1 could bind to miR-4766-5p to regulate CXCL5 expression. Overexpression of CXCL5 overturned those effects of miR-4766-5p in GC cells. RNA Pull down shown that BGC-823 and SGC-7901 cells, miR-4766-5p specifically binds to LBX2-AS1. Conclusions In short, this study demonstrated that LBX2-AS1 promoted proliferation, migration and invasion through up-regulation CXCL5 mediated by miR-4766-5p in GC. The LBX2-AS1/miR-4766-5p/CXCL5 regulatory axis provides a theoretical basis for the research on lncRNA-directed therapeutics in GC.

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“…Tumors of PDAC patients with higher CXCL5 expression had more intratumoral M2 polarized macrophages, neutrophils, and IgG + plasma cells than patients with lower CXCL5 expression (14). At the same time, necroptotic cells also released CXCL5 to promote cancer cell migration and (15). The combined effect of CXCL5 and the receptor CXCR2-ligand helped establish an immunosuppressive microenvironment in PDAC, which has been reported to be associated with unfavorable survival of PDAC patients (7,16).…”

Section: Discussionmentioning

confidence: 96%

FOLFIRINOX regulated tumor immune microenvironment to extend the survival of patients with resectable pancreatic ductal adenocarcinoma

Shen

et al. 2020

Gland Surg

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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignant tumors worldwide due to its ineffective diagnosis and poor prognosis. The longest median overall survival (OS) to PDAC patients has been provided by FOLFIRINOX. It is essential to identify the mechanisms of FOLFIRINOX to gain new insights for the treatment of PDAC.Methods: We compared gene expression levels of PDAC patients who received neoadjuvant FOLFIRINOX prior to surgery with those of patients who received no neoadjuvant chemotherapy.Bioinformatics analysis was applied to screen differentially expressed genes (DEGs). Three microarray data sets were downloaded to analyze gene expression data between PDAC and adjacent non-tumor tissues.Overlapping DEGs were subjected to Kaplan-Meier survival analysis. The genes relating to poor outcomes and would be decreased after FOLFIRINOX were input into the Oncomine, University of Alabama Cancer (UALCAN), and LinkedOmics databases to analyze the gene expression and regulation networks.Results: A total of 83 differentially expressed genes (DEGs) were screened and subjected to bioinformatics analysis, which indicated FOLFIRINOX influenced the immune microenvironment of PDAC. Seventythree genes significantly associated with the OS of PDAC patients. A Venn diagram revealed CXCL5 and PLAU were related to poor outcomes and would decrease after FOLFIRINOX chemotherapy of PDAC patients. It turned out that CXCL5 participated in the immune response-regulating signaling pathway in PDAC patients.Conclusions: FOLFIRINOX regulated tumor immunity by reducing expression of the immunosuppressive gene CXCL5, laying a foundation for further study of combination therapy of FOLFIRINOX and immunotherapy.

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Necroptosis in pancreatic cancer promotes cancer cell migration and invasion by release of CXCL5

Cited by 88 publications

References 55 publications

Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis

Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis

Long noncoding RNA LBX2-AS1-modulated miR-4766-5p regulates gastric cancer development through targeting CXCL5

FOLFIRINOX regulated tumor immune microenvironment to extend the survival of patients with resectable pancreatic ductal adenocarcinoma

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