RESUMO
We previously reported the frequent overexpression of HOX Antisense Intergenic RNA (HOTAIR) in human cervical cancer, which was significantly correlated with tumor progression and poor prognosis. In the present study, we investigated the detailed biological functions of HOTAIR in cervical cancer. In vitro, upregulation of HOTAIR inhibited apoptosis and promoted cellular proliferation, cell cycle progression, migration, and invasion; on the contrast, downregulation of HOTAIR induced more apoptosis, suppressed cellular proliferation, cell cycle, migration, and invasion. Moreover, a high level of HOTAIR was notably associated with radio-resistance and downregulation of p21 in the primary cultured cervical cancer cells. Further, we demonstrated that elevated HOTAIR could induce radio-resistance via inhibiting p21 in HeLa cells, while knockdown of HOTAIR upregulated p21 and consequentially increased the radio-sensitivity of C33A cells. Consistently, stable knockdown of HOTAIR significantly suppressed tumor growth and sensitized cervical cancer to radiotherapy in vivo. In conclusion, HOTAIR served as an onco-lncRNA in cervical cancer which could enhance various aggressive biological behaviors. Moreover, we proved that HOTAIR execute its functions mainly through inhibiting the p21 expression. These results proposed that targeting HOTAIR might be a potent therapeutic strategy in cervical cancer, especially for those patients who accepted radiotherapy.
Assuntos
RNA Longo não Codificante/biossíntese , Tolerância a Radiação/genética , Neoplasias do Colo do Útero/genética , Quinases Ativadas por p21/biossíntese , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/radioterapiaRESUMO
We previously reported frequent loss of microRNA-218 (miR-218) in cervical cancer, which was associated with tumor progression and poor prognosis. As microRNAs were found invovled in the regulation of radiosensitivity in various human cancers, we therefore aim to investigate the effects of miR-218 on radiosensitivity of cervical cancer in the present study. The clonogenic survival assay demonstrated that loss of miR-218 could predict radioresistance in the primary cervical cancer cells (R(2)=0.6516, P<0.001). In vitro, abundant miR-218 increased the radiosensitivity in cervical cancer cells (P<0.001 for HeLa, P=0.009 for SiHa, P=0.016 for C33A and P=0.01 for CaSki). Upregulation of miR-218 significantly enhanced the radiation-induced apoptosis, which was further enhanced by the combination of miR-218 overexpression and radiation In xenograft growth assay, combination of miR-218 overexpression and radiation notably induced cellular apoptosis and suppressed tumor growth. In conclusion, we demonstrated that miR-218 resensitized cervical cancer cells to radiation via promoting cellular apoptosis. Moreover, we proved that miR-218 as a potent predictor of radiosensitivity in cervical cancer, especially for those patients with loss of miR-218.
