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Loss of zinc-finger protein 143 contributes to tumour progression by interleukin-8-CXCR axis in colon cancer.

ABSTRACT: Several studies have shown that expression of zinc-finger protein 143 (ZNF143) is closely related to tumour progression including colon cancer. However, it remains unclear how ZNF143 expression is related to tumour progression within the tumour microenvironment. Here, we investigated whether ZNF143 expression affects the tumour microenvironment and tumour progression by screening molecules secreted by colon cancer cells stably expressing short-hairpin RNAs against ZNF143 or control RNAs. We observed that secretion of interleukin (IL)-8 was increased when ZNF143 expression was reduced in two colon cancer cell lines. The mRNA and protein levels of IL-8 were increased in cells following ZNF143 knockdown, and this effect was reversed when ZNF143 expression was restored. The Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) and extracellular signal-regulated kinase pathways were also shown to contribute to IL-8 expression in ZNF143-knockdown cells. The expression levels of ZNF143 and IL-8 were inversely correlated with three-dimensionally grown spheroids and colon cancer tissues. THP-1 cells were differentiated when cells were incubated with condition media from colon cancer cell with less ZNF143, drastically. Loss of ZNF143 may contribute to the development of colon cancer by regulating intracellular and intercellular signalling for cell plasticity and the tumour microenvironment respectively.

SUBMITTER: Verma V

PROVIDER: S-EPMC6533486 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Loss of zinc-finger protein 143 contributes to tumour progression by interleukin-8-CXCR axis in colon cancer.

Verma Vikas V Paek A Rome AR Choi Beom-Kyu BK Hong Eun Kyung EK You Hye Jin HJ

Journal of cellular and molecular medicine 20190401 6

Several studies have shown that expression of zinc-finger protein 143 (ZNF143) is closely related to tumour progression including colon cancer. However, it remains unclear how ZNF143 expression is related to tumour progression within the tumour microenvironment. Here, we investigated whether ZNF143 expression affects the tumour microenvironment and tumour progression by screening molecules secreted by colon cancer cells stably expressing short-hairpin RNAs against ZNF143 or control RNAs. We obse ...[more]

PMID: 30933430

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Project description:BackgroundThe clinical manifestation of benign prostatic hyperplasia (BPH) is causally linked to the inflammatory microenvironment and proliferation of epithelial and stromal cells in the prostate transitional zone. The CXC-chemokine interleukin-8 (IL-8) contributes to inflammation. We evaluated the expression of inflammatory cytokines in clinical specimens, primary cultures, and prostatic lineage cell lines. We investigated whether IL-8 via its receptor system (IL-8 axis) promotes BPH.MethodsThe messenger RNA and protein expression of chemokines, including components of the IL-8 axis, were measured in normal prostate (NP; n = 7) and BPH (n = 21), urine (n = 24) specimens, primary cultures, prostatic lineage epithelial cell lines (NHPrE1, BHPrE1, BPH-1), and normal prostate cells (RWPE-1). The functional role of the IL-8 axis in prostate epithelial cell growth was evaluated by CRISPR/Cas9 gene editing. The effect of a combination with two natural compounds, oleanolic acid (OA) and ursolic acid (UA), was evaluated on the expression of the IL-8 axis and epithelial cell growth.ResultsAmong the 19 inflammatory chemokines and chemokine receptors we analyzed, levels of IL-8 and its receptors (CXCR1, CXCR2), as well as, of CXCR7, a receptor for CXCL12, were 5- to 25-fold elevated in BPH tissues when compared to NP tissues (P ≤ .001). Urinary IL-8 levels were threefold to sixfold elevated in BPH patients, but not in asymptomatic males and females with lower urinary tract symptoms (P ≤ .004). The expression of the IL-8 axis components was confined to the prostate luminal epithelial cells in both normal and BPH tissues. However, these components were elevated in BPH-1 and primary explant cultures as compared to RWPE-1, NHPrE1, and BHPrE1 cells. Knockout of CXCR7 reduced IL-8, and CXCR1 expression by 4- to 10-fold and caused greater than or equal to 50% growth inhibition in BPH-1 cells. Low-dose OA + UA combination synergistically inhibited the growth of BPH-1 and BPH primary cultures. In the combination, the drug reduction indices for UA and OA were 16.4 and 7852, respectively, demonstrating that the combination was effective in inhibiting BPH-1 growth at significantly reduced doses of UA or OA alone.ConclusionThe IL-8 axis is a promotor of BPH pathogenesis. Low-dose OA + UA combination inhibits BPH cell growth by inducing autophagy and reducing IL-8 axis expression in BPH-epithelial cells.

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Loss of zinc-finger protein 143 contributes to tumour progression by interleukin-8-CXCR axis in colon cancer.

Publications

Loss of zinc-finger protein 143 contributes to tumour progression by interleukin-8-CXCR axis in colon cancer.

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