Dataset Information

Upregulation of STAT1-CCL5 axis is a biomarker of colon cancer and promotes the proliferation of colon cancer cells.

ABSTRACT:

Background

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women globally. Investigating genetic ground differences between normal and CRC tissues would be significant for identifying some key oncogenic pathways and developing anti-cancer agents.

Methods

Weighted gene co-expression network analysis (WGCNA) method was used to screen out core pathways related to the clinical traits of CRC patients. Then, multiple databases were utilized to further verify the hub genes obtained from data mining. Finally, to explore the role of hub genes in CRC, cell counting and EdU assays were performed.

Results

The results of the WGCNA analysis showed that a module (turquoise module) was highly related with CRC differentiation grade (R =0.53, P<0.0001). Enrichment analysis indicated that genes of the turquoise module were remarkably enriched in multiple inflammatory processes and pathways. Among all hub genes of the turquoise module, the mRNA levels of STAT1 and CCL5 were significantly higher in CRC than in normal colon tissues. STAT1 expression was highly positively correlated with the level of CCL5. The results of the cell counting, EdU, CCK-8, and CFSE staining assays showed that interfering with STAT1 and CCL5 could inhibit the proliferation of CRC cells.

Conclusions

Our study indicated that the STAT1-CCL5 axis is an important modulator in the development of CRC through promoting cell proliferation. Moreover, the levels of STAT1 and CCL5 might be valuable biomarkers for CRC screening.

SUBMITTER: Niu M

PROVIDER: S-EPMC7475405 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Upregulation of STAT1-CCL5 axis is a biomarker of colon cancer and promotes the proliferation of colon cancer cells.

Niu Mengke M Yi Ming M Dong Bing B Luo Suxia S Wu Kongming K

Annals of translational medicine 20200801 15

<h4>Background</h4>Colorectal cancer (CRC) is the third most commonly diagnosed cancer in men and women globally. Investigating genetic ground differences between normal and CRC tissues would be significant for identifying some key oncogenic pathways and developing anti-cancer agents.<h4>Methods</h4>Weighted gene co-expression network analysis (WGCNA) method was used to screen out core pathways related to the clinical traits of CRC patients. Then, multiple databases were utilized to further veri ...[more]

PMID: 32953751

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Project description:BackgroundResearch has indicated that the emergence of Schwann cells around premalignant lesions of colon cancer might be an early indicator promoting the onset of tumorigenesis. The present study explored the communication between colon cancer cells and Schwann cells.MethodsImmunofluorescence analyses were conducted to examine the differential distribution of Schwann cells within colon cancer tissues and normal colon tissues. CCK8 assay, colony formation assay, wound healing assay, and transwell assay were performed to investigate the interaction between colon cancer cells and Schwann cells. Exosomes derived from colon cancer cells were isolated to further explore the effect of colon cancer cells on Schwann cells. Gain- and loss-of function experiments, luciferase reporter assays, chromatin immunoprecipitation assays, and immunohistochemistry assays were performed to reveal the cross-talk between colon cancer cells and Schwann cells. Furthermore, colon cancer cells co-cultured with Schwann cells were transplanted into nude mice for evaluating their effect on tumor proliferation and metastasis in vivo.ResultsThe clinicopathological characteristics indicated that Schwann cells were enriched in colon cancer tissues and were associated with tumor metastasis and poor prognosis. The co-culture of Schwann cells with colon cancer cells promoted the proliferation and migration of colon cancer cells and Schwann cells, which was mediated by nerve growth factor (NGF) secreted from Schwann cells. Exosomal miR-21-5p released by colon cancer cells inhibited VHL expression in Schwann cells, which in turn stabilized the HIF-1α protein and increased the transcription of NGF. Meanwhile, the Schwann cells-derived NGF activated TrkA/ERK/ELK1/ZEB1 signaling pathway in colon cancer cells, which further enhanced the expression of exosomal miR-21-5p. Inhibition of either NGF or miR-21-5p significantly inhibited the proliferation and metastasis of transplanted colon cancer cells in nude mice. Coincidently, miR-21-5p was positively associated with the expression of NGF, p-ERK, p-ELK1, and ZEB1 in human colon cancer tissues.ConclusionsOur results implicated a reciprocal communication between colon cancer cells and Schwan cells that promoted the proliferation and metastasis of colon cancer, and identified NGF and exosomal miR-21-5p as potential therapeutic targets for the treatment of colon cancer.

Dataset Information

Upregulation of STAT1-CCL5 axis is a biomarker of colon cancer and promotes the proliferation of colon cancer cells.

Background

Methods

Results

Conclusions

Publications

Upregulation of STAT1-CCL5 axis is a biomarker of colon cancer and promotes the proliferation of colon cancer cells.

Similar Datasets

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