Abstract
BackgroundHomeobox C6 (HOXC6) plays a part in malignant progression of some tumors. However, the expression of HOXC6 and its clinical significance remains unclear in cervical carcinoma (CC). The purpose of this study is to verify the effects of HOXC6 gene silencing on CC through the TGF-β/smad signaling pathway.MethodsCC tissues and corresponding paracancerous tissues were collected from CC patients with involvement of a series of HOXC6-siRNA, HA-HOXC6 and the TGF-β/smad pathway antagonist. HOXC6 expression was analyzed in six CC cell lines (C-33A, HeLa, CaSki, SiHa, ME-180, and HCC-94) by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The mRNA and protein expression of HOXC6, TGF-β1, TGF-β RII, smad4, smad7, E-cadherin, N-cadherin, Vimentin, ki-67, proliferating cell nuclear antigen (PCNA), p27, and Cyclin D1 were determined by RT-qPCR and western blot analysis. Cell proliferation, apoptosis and cell cycle were detected by MTT assay and flow cytometry, respectively.ResultsHigher positive expression rate of HOXC6 protein was observed in CC tissues and HOXC6 was related to TNM stage, lymphatic metastasis, cancer types, primary lesion diameter, and histological grade of CC. Silencing HOXC6 inhibited epithelial-mesenchymal transition (EMT) (shown as decreased N-cadherin and Vimentin, and increased E-cadherin) through the inactivation of the TGF-β/smad signaling pathway. HOXC6 gene silencing hindered cell proliferation and accelerated cell apoptosis of CC cells. Furthermore, the effect of HOXC6 silencing was enhanced when the TGF-β/smad signaling pathway was suppressed.ConclusionThe results reveal that HOXC6 gene silencing may inhibit EMT event and cell viability in CC through the inhibition of the activation of TGF-β/smad signaling pathway.
Highlights
Homeobox C6 (HOXC6) plays a part in malignant progression of some tumors
HOXC6 is upregulated and the TGF‐β/smad4 signaling pathway is activated in CC Immunohistochemistry was used to determine positive expression rate of HOXC6 to analyze the function of HOXC6 in CC
The results of immunohistochemistry showed that: the HOXC6 protein was found in 44 CC tissue samples, with the positive rate of 61.1% and the staining intensity of 3 points; the HOXC6 protein was found in 13 paracancerous tissue samples, with the positive rate of 18.1% and the staining intensity of 1 point
Summary
Homeobox C6 (HOXC6) plays a part in malignant progression of some tumors. The expres‐ sion of HOXC6 and its clinical significance remains unclear in cervical carcinoma (CC). The purpose of this study is to verify the effects of HOXC6 gene silencing on CC through the TGF-β/smad signaling pathway. Cervical carcinoma (CC) remains the second commonest female cancer across the world and prevalently occurs in many low-income countries, mainly caused by persistent infection with human papilloma virus [1]. CC is ranked as the 4th most common cancerrelated death among women, with 88% of all deaths in developing countries [2]. Researches on the potential molecular mechanisms underlying CC progression are urgently needed for effective treatment modalities for CC patients
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