RESUMO
AIM: This study aimed to explore whether the dysregulation of lnc-small nucleolar RNA host gene 1 (SNHG1) and miR-216b-5p correlated with chemoresistance and indicated poor prognosis of serous epithelial ovarian cancer (EOC). METHODS AND RESULTS: The expression of lnc-SNHG1 was upregulated, while miR-216b-5p showed low expression in patients with chemoresistant EOC compared with patients with chemosensitive EOC. The multivariate Cox regression analysis showed that the expression of miR-216b-5p and FIGO stage were independent prognostic factors for the overall survival (OS) of patients with serous EOC. Kaplan-Meier curves revealed a significant association of the increased expression level of lnc-SNHG1 with shorter OS and disease-free survival (DFS). Patients with a low expression level of miR-216b-5p also had shorter OS and DFS. The biological functions were tested using CCK-8 assay, colony formation assay, wound healing assay, and cell apoptosis. The knockdown of SNHG1 and the overexpression of miR-216b-5p stimulated paclitaxel sensitivity in A2780/Taxol cells through inhibiting cell growth and migration and promoting apoptosis. The inhibition of miR-216b-5p could rescue the effect of lnc-SNHG1 inhibition on the sensitivity of A2780/Taxol cells to paclitaxel. Luciferase reporter assay, RNA Binding Protein Immunoprecipitation Assay (RIP), and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) indicated that lnc-SNHG1 acted as a sponge of miR-216b-5p in A2780/Taxol cells. CONCLUSIONS: This study showed that the overexpression of lnc-SNHG1 and decreased expression level of miR-216b-5p correlated with the chemoresistance of patients with serous EOC and indicated shorter OS and DFS. Lnc-SNHG1 functioned as a ceRNA with miR-216b-5p, which was critical in modulating the paclitaxel sensitivity of ovarian cancer cells.
Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , MicroRNAs/biossíntese , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/farmacologia , Prognóstico , RNA Longo não Codificante/biossíntese , RNA Longo não Codificante/genética , Análise de Sobrevida , Transfecção , Regulação para CimaRESUMO
Roles for SOX2 have been extensively studied in several types of cancer, including colorectal cancer, glioblastoma and breast cancer, with particular emphasis placed on the roles of SOX2 in cancer stem cell. Our previous study identified SOX2 as a marker in cervical cancer stem cells driven by a full promoter element of SOX2 EGFP reporter. Here, dual-luciferase reporter and mutagenesis analyses were employed, identifying key cis-elements in the SOX2 promoter, including binding sites for SOX2, OCT4 and NF-YA factors in SOX2 promoter. Mutagenesis analysis provided additional evidence to show that one high affinity-binding domain CCAAT box was precisely recognized and bound by the transcription factor NF-YA. Furthermore, overexpression of NF-YA in primitive cervical cancer cells SiHa and C33A significantly activated the transcription and the protein expression of SOX2. Collectively, our data identified NF-YA box CCAAT as a key cis-element in the SOX2 promoter, suggesting that NF-YA is a potent cellular regulator in the maintenance of SOX2-positive cervical cancer stem cell by specific transcriptional activation of SOX2.
