Dataset Information

The Multifunction Of miR-218-5p-Cx43 Axis In Breast Cancer.

ABSTRACT:

Background

Gemcitabine is proven to be the first-line standard treatment of breast cancers. Yet, little is known involving gemcitabine resistance and remains largely to be elucidated.

Materials and methods

We evaluated the expression of Cx43 in gemcitabine-resistant cells and parental cells by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses. Dual-luciferase reporter assay was applied to examine the epigenetic regulator of Cx43. The role of miR-218-5p-Cx43 axis on cell cytotoxicity, cell proliferation, colony formation, chemoresistance and migration was detected via mammalian expression vector and small short RNA (shRNA) transfection in vitro.

Results

In this study, we found that Cx43 expression levels were significantly lower in gemcitabine-resistant cells than in the parental cells. On deep investigation of the epigenetic regulation of Cx43, a few miRNA candidates targeting Cx43 were derived. Through dual-luciferase reporter assay, Cx43 was proved to be a direct target of miR-218-5p. Besides, qPCR, Western blot demonstrated an inverse correlation between miR-218-5p and Cx43 expression in breast cancer cells, thus forming the miR-218-5p-Cx43 axis. Notably, miR-218-5p-Cx43 axis was found to be involved in the process of gemcitabine chemoresistance, cell proliferation and migration in breast cancer cells.

Conclusion

Our findings suggested that miR-218-5p-Cx43 axis was versatile and indicated significant potency in breast cancer cells. More importantly, miR-218-5p-Cx43 axis might be valuable in translational medicine, with therapeutic and prognostic information.

SUBMITTER: Xia C

PROVIDER: S-EPMC6790128 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPancreatic cancer is a highly lethal malignancy with poor prognosis. Anillin (ANLN), an actin binding protein, is upregulated and plays an important role in many malignant tumors. However, the precise role of ANLN in pancreatic cancer remains unclear.MethodsThe expression of ANLN and its association with pancreatic cancer patient survival were analyzed using an online database and confirmed by immunohistochemistry. The ANLN protein expression in pancreatic cancer cell lines was detected by Western blot. Cell proliferation, colony formation and transwell assays in vitro and in vivo tumor growth were used to determine the role of ANLN in pancreatic cancer. Gene expression microarray analysis and a series of in vitro assays were used to elucidate the mechanisms of ANLN regulating pancreatic cancer progression.ResultsWe found that the ANLN expression was significantly upregulated in pancreatic cancer tissues and cell lines. The high expression of ANLN was associated with tumor size, tumor differentiation, TNM stage, lymph node metastasis, distant metastasis and poor prognosis in pancreatic cancer. ANLN downregulation significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenicity in nude mice. Meanwhile, we found that ANLN knockdown inhibited several cell-cell adhesion related genes, including the gene encoding LIM and SH3 protein 1 (LASP1). LASP1 upregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression. Moreover, we found that ANLN downregulation induced the expression of miR-218-5p which inhibited LASP1 expression through binding to its 3'UTR. We also found that ANLN-induced enhancer of zeste homolog 2 (EZH2) upregulation was involved in regulating miR-218-5p/LASP1 signaling axis. EZH2 upregulation or miR-218-5p downregulation partially reversed the tumor-suppressive effect of ANLN downregulation on pancreatic cancer cell progression.ConclusionANLN contributed to pancreatic cancer progression by regulating EZH2/miR-218-5p/LASP1 signaling axis. These findings suggest that ANLN may be a candidate therapeutic target in pancreatic cancer.