CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer via Inhibiting JAK-STAT Signaling Pathway

Abstract

PurposeThis study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).MethodsBioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.ResultsCXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors via activation of JAK-STAT signaling pathway.ConclusionCXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.

Transcriptomic analysis of plasma exosomes provides molecular information of response to cabazitaxel treatment in men with metastatic castration‐resistant prostate cancer

“…Recently it has been shown that cabazitaxel can affect the immune system and is associated with macrophage induction and M2 polarization, thus we investigated if we could identify differences between the two groups of patients at baseline. [23][24][25] Interestingly, we found a variety of immune related pathways enriched in nonresponders compared to responders at baseline (Figure 1G). We found the pathways including Fcγ receptor-mediated phagocytosis in macrophages and monocytes, as well as interleukin (IL)-8, CXCR4 and IL-3 signaling (Figure 1G).…”

RSRC2 Expression Inhibits Malignant Progression of Triple-Negative Breast Cancer by Transcriptionally Regulating SCIN Expression

“…Further, the in vitro experiment demonstrated that RSRC2 could inhibit the MDA-MB-231 cells and MDA-MB-453 cells clonogenic ability, adhesion, migration and invasion ability. The transcriptome array data analysis identified differentially expressed genes in the MDA-MB-231 shRSRC2 cells and control cells and identified SCIN, IL6, CXCL8, CXCL1, PTGS2, IL1B, NOS3, ICAM1, moesin and DCAF6, which were reported to be involved in cell proliferation, migration and cell adhesion [ 15 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The intersection set analysis of the bioinformatics database and transcriptome array data identified six common genes, FSTL1, GDF15, IQSEC2, KDM3A, LTC4S and TCTEX1D4, in which most of them were involved in tumor cell proliferation and growth [ 29 , 30 , 31 , 32 , 33 , 34 ].…”

CXCL1: Gene, Promoter, Regulation of Expression, mRNA Stability, Regulation of Activity in the Intercellular Space

“…Notably, in non-cancer cells, where there is no high basal NF-κB activation, transcriptional regulation plays a major role in regulating CXCL1 expression [ 37 ]. Additionally, no less important for CXCL1 mRNA stability are miRNAs, which cause the decay of this transcript [ 112 , 113 , 114 , 115 , 116 , 117 ]. All of the factors mentioned in this section lead to the degradation or improvement in the stability of CXCL1 mRNA.…”

“…In ovarian cancer, renal cancer [ 112 ] and hepatocellular carcinoma [ 114 ], there is a downregulation of the miR-200 family [ 112 ]; in ovarian cancer there is a downregulation of miR-27b-5p [ 116 ]; and in gastric cancer, there is a downregulation of miR-204 [ 115 ]. Other examples include miR-302e in colorectal cancer [ 117 ] and miR-141 in non-small cell lung cancer [ 113 ].…”