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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 expression is negatively related to radioresistance in HR-HPV (+) cervical cancer. (A, C) qRT-PCR analysis of relative miR-375 expression in serum (A) and tissue (C) of cervical cancer patients (n=22) and healthy controls (n=20). Relative miR-375 expression was significantly higher in serum (A) and tissue (C) of HR-HPV (+) cervical cancer patients than in healthy controls. (B, D) qRT-PCR analysis showed that miR-375 expression was even lower in both serum (B) and tissue (D) of radioresistant patients (n=13) than in radiosensitive patients (n=9). (E) The surviving fraction of HPV-18-positive HeLa cells was significantly lower than in HPV-16-positive SiHa cells under radiation treatment. (F) qRT-PCR analysis showed that miR-375 expression was significantly lower in SiHa cells than in HeLa cells. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.
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f1-medscimonit-21-2210: MiR-375 expression is negatively related to radioresistance in HR-HPV (+) cervical cancer. (A, C) qRT-PCR analysis of relative miR-375 expression in serum (A) and tissue (C) of cervical cancer patients (n=22) and healthy controls (n=20). Relative miR-375 expression was significantly higher in serum (A) and tissue (C) of HR-HPV (+) cervical cancer patients than in healthy controls. (B, D) qRT-PCR analysis showed that miR-375 expression was even lower in both serum (B) and tissue (D) of radioresistant patients (n=13) than in radiosensitive patients (n=9). (E) The surviving fraction of HPV-18-positive HeLa cells was significantly lower than in HPV-16-positive SiHa cells under radiation treatment. (F) qRT-PCR analysis showed that miR-375 expression was significantly lower in SiHa cells than in HeLa cells. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.

Mentions: Based on serum and tumor tissue samples from the cervical cancer patients and healthy controls, qRT-PCR results showed that miR-375 expression was significantly lower in the cancer patients than in the controls (Figure 1A, 1C). Its expression was even lower in radioresistant patients than in radiosensitive patients (Figure 1B, 1D). HPV-16-positive SiHa, which had lower response to radiation than HPV-18-positive HeLa cells (Figure 1E), also had lower expression of miR-375 (Figure 1F). These results suggest that miR-375 might be involved in the radioresistance of HPV (+) cervical cancer.


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 expression is negatively related to radioresistance in HR-HPV (+) cervical cancer. (A, C) qRT-PCR analysis of relative miR-375 expression in serum (A) and tissue (C) of cervical cancer patients (n=22) and healthy controls (n=20). Relative miR-375 expression was significantly higher in serum (A) and tissue (C) of HR-HPV (+) cervical cancer patients than in healthy controls. (B, D) qRT-PCR analysis showed that miR-375 expression was even lower in both serum (B) and tissue (D) of radioresistant patients (n=13) than in radiosensitive patients (n=9). (E) The surviving fraction of HPV-18-positive HeLa cells was significantly lower than in HPV-16-positive SiHa cells under radiation treatment. (F) qRT-PCR analysis showed that miR-375 expression was significantly lower in SiHa cells than in HeLa cells. 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

f1-medscimonit-21-2210: MiR-375 expression is negatively related to radioresistance in HR-HPV (+) cervical cancer. (A, C) qRT-PCR analysis of relative miR-375 expression in serum (A) and tissue (C) of cervical cancer patients (n=22) and healthy controls (n=20). Relative miR-375 expression was significantly higher in serum (A) and tissue (C) of HR-HPV (+) cervical cancer patients than in healthy controls. (B, D) qRT-PCR analysis showed that miR-375 expression was even lower in both serum (B) and tissue (D) of radioresistant patients (n=13) than in radiosensitive patients (n=9). (E) The surviving fraction of HPV-18-positive HeLa cells was significantly lower than in HPV-16-positive SiHa cells under radiation treatment. (F) qRT-PCR analysis showed that miR-375 expression was significantly lower in SiHa cells than in HeLa cells. Each bar represents the mean ±S.D. of 3 experiments. * P<0.05; ** P<0.01, *** P<0.001.
Mentions: Based on serum and tumor tissue samples from the cervical cancer patients and healthy controls, qRT-PCR results showed that miR-375 expression was significantly lower in the cancer patients than in the controls (Figure 1A, 1C). Its expression was even lower in radioresistant patients than in radiosensitive patients (Figure 1B, 1D). HPV-16-positive SiHa, which had lower response to radiation than HPV-18-positive HeLa cells (Figure 1E), also had lower expression of miR-375 (Figure 1F). These results suggest that miR-375 might be involved in the radioresistance of HPV (+) cervical cancer.

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