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Objective:To investigate the value of serum miR-143 level combined with MRI in predicting the early response to concurrent chemoradiotherapy (CCRT) in cervical cancer.Methods:A total of 85 patients with pathologically confirmed cervical cancer underwent conventional MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The biopsy tissues and serum samples were collected. The differential expression of miRNA in the biopsy tissues was determined by microarray chip. The expression level of miR-143 in the serum samples was analyzed by qRT-PCR. All patients were divided into the non-residual and residual tumor groups according to post-treatment MRI. Pre-treatment clinical factors, MRI parameters and miR-143 between two groups were statistically analyzed by the univariate and multivariate analyses. The optimal thresholds and predictive performance for post-treatment incidence of residual tumors were estimated by drawing the ROC curve.Results:At one month after CCRT, there were 52 patients in the non-residual tumor group and 33 patients in the residual tumor group. In the residual tumor group, pre-treatment FIGO staging, apparent diffusion coefficient (ADC), D and V e were significantly higher (all P<0.05), whereas K trans value was significantly lower ( P<0.001) when compared to those in the non-residual tumor group. The miRNA array analysis showed that there were 16 miRNAs with differential expression levels between two groups (all P<0.05). Among them, the increase of miR-143 was the most significant in the residual tumor group. Compared with the residual tumor group, the expression level of serum miR-143 was significantly down-regulated in the non-residual tumor group ( P=0.002). Compared with the SiHa cells, the expression level of miR-143 in the SiHa-R cells was significantly up-regulated ( P<0.05). Multivariate analysis showed that only miR-143, D, K trans and V e were the independent prognostic factors. The combination of multi-parametric MRI and miR-143 exhibited the highest predictive performance (AUC=0.975), with a sensitivity of 84.8% and a specificity of 96.2%. Conclusion:The combination of multi-parametric MRI with miR-143 further improves the predictive performance for residual tumors after CCRT, which contributes to the personalized treatment of cervical cancer.
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Objective:To investigate the effect of LINC00261 on the radiosensitivity of nasopharyngeal carcinoma and tumor formation and its underlying mechanism in nude mice.Methods:qRT-PCR was used to detect the relative expression levels of miR-620 and LINC00261 in radiosensitive and radioresistant nasopharyngeal carcinoma tissues. After the 6-10B and HNE-3 cells were irradiated with 0, 2, 4, 6, and 8 Gy 60Coγ-ray, the relative expression levels of miR-620 and LINC00261 were measured by qRT-PCR. After over-expression or silencing of LINC00261 and inhibition of miR-620 expression, the cells were irradiated with 4 Gy 60Coγ-ray. Clone formation assay was performed to detect the radiosensitivity of nasopharyngeal carcinoma cells. Flow cytometry was used to detect cell apoptosis. Western blot was utilized to detect the expression levels of Cleaved caspase-3 and Cleaved caspase-9 proteins. Luciferase reporter assay was adopted to analyze the targeting relationship between LINC00261 and miR-620. The changes in tumor formation were observed in tumor-bearing nude mice. Results:Compared with the radiosensitive tissues, the expression of LINC00261 was significantly down-regulated, whereas that of miR-620 was significantly up-regulated in radioresistant tissues (both P<0.05). After different doses of irradiation, the expression of LINC00261 was significantly down-regulated, whereas that of miR-620 was significantly up-regulated in 6-10B and HNE-3 cells (both P<0.05). After overexpression of LINC00261 and interference with miR-620 expression, the expression levels of Cleaved caspase-3 and Cleaved caspase-9 were significantly up-regulated (both P<0.05), the cell apoptosis rate was remarkably increased ( P<0.05) and the cell survival fraction was significantly enhanced in 6-10B and HNE-3 cells ( P<0.05). LINC00261 targetedly regulated the expression of miR-620. Overexpression of miR-620 could attenuate the radiosensitization and pro-apoptotic effects of LINC00261 overexpression on nasopharyngeal carcinoma cells. LINC00261 overexpression could significantly reduce the tumor formation weight of nasopharyngeal carcinoma in nude mice ( P<0.05). Conclusion:Overexpression of LINC00261 can increase the radiosensitivity of nasopharyngeal carcinoma cells probably by targeted regulation of miR-620 expression.
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Objective To explore whether MiR-129-5p participates in radiosensitivity of medullary thyroid cell MZ-CRC-1 by inhibiting the gene expression of high mobility group protein B1 ( HMGB1) . Methods The radioresistant cell line MZ-CRC-1/R was established from MZ-CRC-1. Cell survival fraction was analyzed by colony formation assay. The expressions of miR-129-5p in MZ-CRC-1 and MZ-CRC-1/R cells were detected by qRT-PCR. Cell viability was determined by MTT assay. Cell apoptosis was measured by flow cytometry. Dual-luciferase reporter assay was performed to confirm the relationship between miR-129-5p and HMGB1. Besides, the protein expressions of HMGB1 and p-AKt were evaluated by western blot. Results Compared with that of MZ-CRC-1 cells, the survival fraction of MZ-CRC-1/R cells was significantly increased (t=3. 038, 4. 330, 4. 885, 4. 568, P<0. 05), the cell viability of MZ-CRC-1/R cells was also increased ( t=3. 637, 7. 734, 11. 896, 14. 522, P<0. 05) , and the expression of miR-129-5p(0.26±0.03) was significantly decreased in MZ-CRC-1/R cells(1.00±0.06) (t=19. 107, P<0. 05) . Compared with miR-NC-inhibitor group, cell viability was promoted and cell apoptosis was blocked in the miR-129-5p-inhibitor group ( t=5. 156, 6. 005, 9. 649, 8. 659, P<0. 05) . Moreover, miR-129-5p mimic suppressed cell viability and enhanced cell apoptosis after irradiation ( t=3. 118, 5. 034, 6. 005, 7. 488, 6. 362, P<0. 05) . Overexpression of miR-129-5p inhibited the protein expressions of HMGB1 and p-AKt (t=9. 325, 10. 614, P<0. 05). In addition, HMGB1 depletion rescued cell apoptosis that was reduced by miR-129-5p inhibitor in MZ-CRC-1 cells ( t=6. 700, P<0. 05) , while HMGB1 overexpression attenuated the effect of miR-129-5p upregulation on MZ-CRC-1/R cells ( t=7. 073,P<0. 05) . Conclusions miR-129-5p increased the radiosensitivity of medullary thyroid-like cell MZ-CRC-1 by inhibiting HMGB1.