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Oncol Lett. 2017 Dec;14(6):7910-7916. doi: 10.3892/ol.2017.7260. Epub 2017 Oct 23.

Human thymic stromal lymphopoietin promotes the proliferation and invasion of cervical cancer cells by downregulating microRNA-132 expression.

Author information

1
Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.
2
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.
3
Medical Center of Diagnosis and Treatment for Cervical Diseases, Hospital of Obstetrics and Gynecology, Fudan University, Shanghai 200011, P.R. China.

Abstract

Thymic stromal lymphopoietin (TSLP), produced by cervical cancer (CC) cells, promotes angiogenesis, and the recruitment and functional regulation of eosinophils. It has been reported that microRNA (miR)-132 is aberrantly decreased in CC tissues. However, the function and mechanism of TSLP on the biological behaviors of CC cells is largely unknown. The aim of the present study was to investigate the effect of TSLP on the expression of miR-132 and the proliferation and invasion in vitro of CC cell lines, namely, HeLa and SiHa cells. The transcrpitional level of miR-132 was analyzed using reverse transcription-quantitative polymerase chaon reaction. The proliferation, invasion, and the expression of proliferation and invasion-related molecules in HeLa and SiHa cells in vitro were evaluated using bromodeoxyuridine cell proliferation, Matrigel invasion assays, flow cytometry and ELISA, respectively. Here, it was revealed that recombinant human TSLP (rhTSLP) downregulated the expression levels of miR-132 in HeLa and SiHa cells, and by contrast, the neutralizing antibodies for TSLP or TSLP receptor (TSLPR) upregulated miR-132 expression levels in HeLa and SiHa cells. The overexpression of miR-132 resulted in a lowered proliferation and invasiveness, decreased levels of proliferation-associated molecules marker of proliferation Ki-67 and proliferating cell nuclear antigen, and the decreased production of matrix metalloproteinase (MMP)2 and MMP9 in HeLa and SiHa cells. Compared with the control group, there was a higher level of proliferation and invasion in HeLa and SiHa cells following stimulation with rhTSLP. However, these effects induced by rhTSLP were significantly impaired in HeLa and SiHa cells with miR-132 overexpression. The results of the present study indicated that TSLP produced by CC cells downregulated miR-132 expression, and stimulated the proliferation and invasion of CC cells, thereby further promoting the development of CC.

KEYWORDS:

cervical cancer cells; invasion; microRNA-132; proliferation; thymic stromal lymphopoietin

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