CCL3-CCR5 axis promotes cell migration and invasion of colon adenocarcinoma via Akt signaling pathway.

BACKGROUND: Infiltration of tumor-associated macrophages (TAMs) can promote tumorigenesis and development. C-C motif chemokine ligand 3 (CCL3) was reported to be derived from TAMs and tumor cells and facilitate the progression of several cancers. Nevertheless, whether CCL3 can be derived from TAMs and tumor cells of colon adenocarcinoma (COAD) is unclarified. METHODS: Peripheral blood monocytes-derived macrophages were polarized by the conditioned medium from COAD cells to establish TAM-like macrophages (TAM1/2). RT-qPCR and western blotting were used for detection of expression levels of CCL3 and its receptors C-C motif chemokine receptor 1 (CCR1) and CCR5 in TAM1/2 and COAD cells. Immunofluorescence staining was utilized for evaluating CCL3, CD163 and CCR5 expression. The Akt signaling pathway-associated protein levels were measured by western blotting. Transwell assays were used for assessing cell migration and invasiveness. RESULTS: CCL3 displayed a high level in TAMs and cancer cells of COAD. CCL3 activated the Akt signaling pathway by binding to CCR5. CCL3-CCR5 axis facilitated COAD cell migration and invasiveness by activating the Akt signaling. CCL3 derived from both TAMs and cancer cells contributed to the malignant behaviors of COAD cells. High expression of CCL3/CCR5 was closely associated with poor prognoses of COAD patients. CONCLUSION: CCL3-CCR5 interaction promotes cell migration and invasiveness, and functions as a prognostic biomarker for COAD.

RNA-binding protein RBM38 inhibits colorectal cancer progression by partly and competitively binding to PTEN 3'UTR with miR-92a-3p.

RNA-binding motif protein 38 (RBM38) belongs to the RNA recognition motif family of RNA-binding proteins (RBPs). RBM38 was previously identified to suppress tumorigenesis in colorectal cancer (CRC). RBM38 was also reported to bind to the 3'UTR of phosphatase and tensin homolog gene on chromosome 10 (PTEN), a tumor suppressor involved in many cellular processes, to stabilize PTEN transcripts. In the present study, we investigated the mechanisms underlying the regulation of RBM38 in CRC. Reverse transcription quantitative polymerase chain reaction and western blotting detected the expression of RBM38, PTEN, and miR-92a-3p. Colony formation, EdU, sphere formation, Transwell invasion, and in vivo assays examined the influence of RBM38 on CRC progression. Furthermore, RNA immunoprecipitation (RIP) assay determined the binding site of RBM38 on PTEN 3'UTR. The binding of miR-92a-3p or RBM38 on PTEN 3'UTR was assessed by luciferase reporter and RIP assays. We discovered that RBM38 was downregulated in CRC cells and tissues. RBM38 repressed CRC progression in vitro and in vivo. Furthermore, RBM38 upregulated and stabilized PTEN expression. Interestingly, the overexpression of PTEN reversely attenuated the promotion of RBM38 depletion on CRC progression. Additionally, RBM38 competed with miR-92a-3p in binding to PTEN 3'UTR. In conclusion, RBM38 inhibits CRC progression by competitively binding to PTEN 3'UTR with miR-92a-3p.