Overexpression of microRNA-132 enhances the radiosensitivity of cervical cancer cells by down-regulating Bmi-1

Abstract

We examined the effects of microRNA-132 (miR-132) on Bmi-1 expression and radiosensitivity in HeLa, SiHa, and C33A cervical cancer (CC) cells and 104 CC patients. MiR-132 expression was decreased and Bmi-1 expression was increased in tumor tissues compared to adjacent normal tissues and in radiotherapy-resistant patients compared to radiotherapy-sensitive patients. MiR-132 expression and Bmi-1 mRNA expression were also negatively correlated in tumor tissues. HeLa, SiHa, and C33A cells were divided into blank, miR-132 negative control (NC), miR-132 inhibitor, miR-132 mimics, siBmi-1, and miR-132 inhibitor + siBmi-1 groups, after which expression of miR-132 and Bmi-1, and the interaction between them and cell survival, proliferation, and apoptosis were examined. Bmi-1 was confirmed as a target of miRNA-132. Survival was higher and apoptosis lower in the miR-132 inhibitor group than the blank group after various doses of radiation. By contrast, survival was lower and apoptosis higher in the miRNA-132 mimics and siBmi-1 groups than in the blank group. Moreover, miR-132 expression increased and Bmi-1 mRNA expression decreased in each group at radiation doses of 6 and 8 Gy. Finally, co-administration of radiotherapy and exogenous miR-132 inhibited the growth of HeLa cell transplant-induced tumors in nude mice more effectively than radiotherapy alone. These results suggest overexpression of miR-132 enhances the radiosensitivity of CC cells by down-regulating Bmi-1 and that miR-132 may be a useful new target for the treatment of CC.

Combination of RIZ1 Overexpression and Radiotherapy Contributes to Apoptosis and DNA Damage of HeLa and SiHa Cervical Cancer Cells

“…According to previous studies, the patients with cervical squamous cell carcinoma and adenocarcinoma carcinoma treated with definitive radiotherapy exhibited different survival outcome, sensitivity to radiation and prognosis . However, our results did not reveal the obvious difference in radiosensitivity between HeLa and SiHa cells, which can also be found in several similar studies . This discrepancy may be because the efficacy of radiotherapy on patients is affected by many factors in vivo , while fewer factors are going to affect the cells' exposed to radiation in vitro .…”

<p>MiR-499a-5p Inhibits Pr5/4/20 publish l Cancer Cells via Targeting eIF4E</p>

“…For example, Liu et al found that miR-132 was downregulated in radiotherapy-sensitive CC patients and cells, and inhibited proliferation and promoted apoptosis and radiosensitivity of CC cells by targeting Bmi-1. 21 Wu et al exhibited that miR-15a-3p was increased in radiation-exposed CC cells and overexpression of miR-15a-3p sensitized CC to irradiation by inhibiting tumor protein D52. 22 Our data demonstrated that eIF4E overexpression abolished radiosensitization induced by transfection of miR-499a-5p mimic in CC cells.…”

Value of Diffusion-Weighted Magnetic Resonance Imaging Combined with miR-18a Level in Predicting Radiosensitivity of Cervical Cancer

“…miRNAs can play important roles in tumor proliferation, progression, and metastasis by modulating the expression of certain target genes [ 20 , 21 ], and some of them can be regarded as reliable biomarkers for prediction of prognosis and curative response in various cancers [ 22 ]. miR-18a, miR-132, and miR-145 have been reported to affect the radiosensitivity of cervical cancer [ 11 – 13 ]. In the present study, we compared the expression of these miRNAs between cervical cancer tissues and normal tissues.…”

“…MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs that play critical roles in tumor proliferation, progression, and metastasis [ 10 ]. Previous studies have revealed that many miRNAs participate in biological responses of cervical cancer, and miR-18a, miR-132, and miR-145 have been reported to modulate the radiosensitivity of cervical cancer cells [ 11 – 13 ]. Therefore, miRNAs can also be regarded as reliable predictors for cervical cancer radiosensitivity.…”