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miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway.

Song L, Liu S, Zeng S, Zhang L, Li X - Med. Sci. Monit. (2015)

Bottom Line: HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression.The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression.UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).

ABSTRACT

Background: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer.

Material and methods: qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models.

Results: The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.

Conclusions: The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.

No MeSH data available.


Related in: MedlinePlus

MiR-375 modulates radiation-induced apoptosis of HR-HPV (+) cervical cancer cells. (A, C) qRT-PCR analysis confirmed successful transfection of miR-375 into HeLa (A) and SiHa (C) cells. (B, D) Transfection of miR-375 mimics significantly increased radiosensitivity in both HeLa (B) and SiHa (D) cells. (E) Representative images of flow cytometry analysis of apoptotic HeLa and SiHa cells by staining active caspase-3 at 48 h after radiation treatment. (F) (J) Quantification of the apoptotic HeLa and SiHa cells at 48 h after transfection or 48 h after 8Gy treatment. miR-375 overexpression significantly increased the proportion of apoptotic cells treated by radiation. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.
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f2-medscimonit-21-2210: MiR-375 modulates radiation-induced apoptosis of HR-HPV (+) cervical cancer cells. (A, C) qRT-PCR analysis confirmed successful transfection of miR-375 into HeLa (A) and SiHa (C) cells. (B, D) Transfection of miR-375 mimics significantly increased radiosensitivity in both HeLa (B) and SiHa (D) cells. (E) Representative images of flow cytometry analysis of apoptotic HeLa and SiHa cells by staining active caspase-3 at 48 h after radiation treatment. (F) (J) Quantification of the apoptotic HeLa and SiHa cells at 48 h after transfection or 48 h after 8Gy treatment. miR-375 overexpression significantly increased the proportion of apoptotic cells treated by radiation. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.

Mentions: To explore the influence of miR-375 expression on radiation-induced apoptosis, SiHa and HeLa cells were transfected for miR-375 overexpression (Figure 2A, 2C). miR-375 overexpression conferred significantly reduced survival under radiation treatment of both cell lines (Figure 2B, 2D). By measuring the apoptotic marker caspase 3, we observed that the ratios of radiation-induced apoptotic SiHa or HeLa cells with miR-375 overexpression were significantly higher than the corresponding negative controls (Figure 2E, 2F). These results suggest that miR-375 can directly modulate apoptosis of HR-HPV (+) cervical cancer cells induced by radiation.


miR-375 Modulates Radiosensitivity of HR-HPV-Positive Cervical Cancer Cells by Targeting UBE3A through the p53 Pathway.

Song L, Liu S, Zeng S, Zhang L, Li X - Med. Sci. Monit. (2015)

MiR-375 modulates radiation-induced apoptosis of HR-HPV (+) cervical cancer cells. (A, C) qRT-PCR analysis confirmed successful transfection of miR-375 into HeLa (A) and SiHa (C) cells. (B, D) Transfection of miR-375 mimics significantly increased radiosensitivity in both HeLa (B) and SiHa (D) cells. (E) Representative images of flow cytometry analysis of apoptotic HeLa and SiHa cells by staining active caspase-3 at 48 h after radiation treatment. (F) (J) Quantification of the apoptotic HeLa and SiHa cells at 48 h after transfection or 48 h after 8Gy treatment. miR-375 overexpression significantly increased the proportion of apoptotic cells treated by radiation. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4524565&req=5

f2-medscimonit-21-2210: MiR-375 modulates radiation-induced apoptosis of HR-HPV (+) cervical cancer cells. (A, C) qRT-PCR analysis confirmed successful transfection of miR-375 into HeLa (A) and SiHa (C) cells. (B, D) Transfection of miR-375 mimics significantly increased radiosensitivity in both HeLa (B) and SiHa (D) cells. (E) Representative images of flow cytometry analysis of apoptotic HeLa and SiHa cells by staining active caspase-3 at 48 h after radiation treatment. (F) (J) Quantification of the apoptotic HeLa and SiHa cells at 48 h after transfection or 48 h after 8Gy treatment. miR-375 overexpression significantly increased the proportion of apoptotic cells treated by radiation. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.
Mentions: To explore the influence of miR-375 expression on radiation-induced apoptosis, SiHa and HeLa cells were transfected for miR-375 overexpression (Figure 2A, 2C). miR-375 overexpression conferred significantly reduced survival under radiation treatment of both cell lines (Figure 2B, 2D). By measuring the apoptotic marker caspase 3, we observed that the ratios of radiation-induced apoptotic SiHa or HeLa cells with miR-375 overexpression were significantly higher than the corresponding negative controls (Figure 2E, 2F). These results suggest that miR-375 can directly modulate apoptosis of HR-HPV (+) cervical cancer cells induced by radiation.

Bottom Line: HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression.The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression.UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Gynaecology and Obstetrics, Cangzhou Central Hospital, Cangzhou, Hebei, China (mainland).

ABSTRACT

Background: Prediction of radioresistance of HR-HPV-positive (+) cervical cancer, especially before the course of radiotherapy, is quite beneficial to develop an optimal treatment strategy for individual patients. Unfortunately, the mechanisms responsible for radioresistance of cervical cancer are still largely unexplored. HR-HPV infection leads to a series of changes to normal biophysical process, including miRNAs expression. In this study, we explored the association between miR-375 and radioresistance in HR-HPV (+) cervical cancer.

Material and methods: qRT-PCR analysis was performed to determine miR-375 expression in HR-HPV-positive (+) cervical cancer patients and in HPV-16-positive SiHa and HPV-18-positive HeLa cervical cancer cell lines. The influence of miR-375 on radiosensitivity and the downstream regulative network were further explored in the cell line models.

Results: The results verified a putative binding site between miR-375 and UBE3A. miR-375 overexpression could significantly reduce UBE3A expression. UBE3A knockdown led to significantly reduced cell survival under radiation treatment. miR-375 promoted radiosensitivity of HR-HPV (+) cancer through decreasing p53 degradation and thereby increasing radiation-induced apoptosis.

Conclusions: The miR-375-UBE3A axis is important in modulating radiosensitivity of HR-HPV (+) cervical cancer.

No MeSH data available.


Related in: MedlinePlus