Dataset Information

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer.

ABSTRACT:

Purpose

Zinc finger SWIM-type containing 5 (ZSWIM5) is a newly discovered protein, which contains a novel zinc-chelating domain SWIM (CxCxnCxH), and is predicted to interact with DNA or proteins. Currently, the knowledge of functions of ZSWIM5 remains limited. In this study, we aimed to elucidate the biological functions of ZSWIM5 and their mechanisms.

Patients and methods

We detected the expression of ZSWIM5 in samples from 139 cases of non-small-cell lung cancer (NSCLC) patients and six cell lines using immunohistochemistry and Western blot. Moreover, we explored the biological functions of ZSWIM5 in lung cancer cells by siRNA interference and cDNA transfection of ZSWIM5.

Results

The results showed that compared with adjacent non-tumor lung tissues, ZSWIM5 expression was significantly decreased in NSCLC tissues (P=0.0199) and that the ZSWIM5-positive rate in non-tumor tissues (76.67%) was notably higher than that in NSCLC tissues (40.29%). ZSWIM5 expression in human normal bronchial epithelial cells was also much higher than that in lung cancer lines (P<0.001). ZSWIM5-negative expression was significantly related to TNM stage (P<0.001), lymph node metastasis (P=0.002), and poor prognosis (P<0.001) of NSCLC patients. MTT and colony formation assays showed that ZSWIM5 could inhibit the proliferation and colony formation abilities of lung cancer cells. Meanwhile, the results of transwell and wound healing assays showed that ZSWIM5 could suppress the invasion and migration of lung cancer cells. Further investigation revealed that ZSWIM5 could downregulate cyclin D1, cyclin E, cyclin A2, MMP2, and MMP9 expression, which affected the proliferation, invasion, and migration abilities of lung cancer cells.

Conclusion

ZSWIM5 could inhibit the malignant progression of NSCLC by affecting the expression of cyclins and MMPs.

SUBMITTER: Xu K

PROVIDER: S-EPMC6130280 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer.

Xu Ke K Liu Bin B Ma Yegang Y Xu Baojin B Xing Xiaojing X

Cancer management and research 20180904

<h4>Purpose</h4>Zinc finger SWIM-type containing 5 (ZSWIM5) is a newly discovered protein, which contains a novel zinc-chelating domain SWIM (CxCxnCxH), and is predicted to interact with DNA or proteins. Currently, the knowledge of functions of ZSWIM5 remains limited. In this study, we aimed to elucidate the biological functions of ZSWIM5 and their mechanisms.<h4>Patients and methods</h4>We detected the expression of ZSWIM5 in samples from 139 cases of non-small-cell lung cancer (NSCLC) patients ...[more]

PMID: 30233241

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Project description:ObjectivemicroRNAs are regulatory molecules regarded as important in the pathogenesis of different types of tumors. microRNA-216a (miR-216a-5p) has been identified as a tumor suppressor in multiple malignancies. However, the role of miR-216a-5p in the pathogenesis of small cell lung cancer (SCLC) remains obscure. The objective of this study was to investigate the role of the miR-216a-5p/Bcl-2 axis in SCLC pathogenesis.Materials and methodsAll the experimental methods used were as follows: microarray analysis, cell culture, transient, and stable gene transfection; real-time fluorescence PCR; Western blot; flow cytometry for cell cycle analysis; in vitro proliferation assay; in vitro wound healing experiment; in vivo xenograft model in nude mice; and dual luciferase reporter assay. All statistical analyses were carried out using GraphPad Prism 7 software. Statistical significance was analyzed by Student's t-test or one-way ANOVA. P <0.05 (typically compared with the negative control group) was considered as significant and is marked with an asterisk in the figures.ResultsIn this study, we observed that miR-216a-5p is downregulated in SCLC cell lines compared to that in the normal human bronchial epithelial cell line 16-HBE. In vitro and in vivo experiments demonstrate that upregulation of miR-216a-5p significantly decreased cell growth and migration and its downregulation increased SCLC cell proliferation and migration and influenced the cell cycle. Using bioinformatics analyses, we predicted that the important antiapoptotic gene Bcl-2 is targeted by miR-216a-5p, and we identified a functional miR-216a-5p binding site in the 3'-UTR of Bcl-2 using luciferase reporter assay. Furthermore, we determined that suppression of miR-216a-5p modulated the expression of Bcl-2, Bax, and Bad proteins (Bcl-2 family proteins), while Bcl-2 knockdown abrogated the effect of miR-216a-5p downregulation on cell proliferation, cell migration, and the cell cycle.ConclusionTaken together, these findings suggest that miR-216a-5p regulates SCLC biology via Bcl-2 family proteins. Therefore, our study highlights the role of the miR-216a-5p/Bcl-2 axis in SCLC pathogenesis.

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Dataset Information

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer.

Purpose

Patients and methods

Results

Conclusion

Publications

A novel SWIM domain protein ZSWIM5 inhibits the malignant progression of non-small-cell lung cancer.

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