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MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells.

Jiang P, Rao EY, Meng N, Zhao Y, Wang JJ - Radiat Oncol (2010)

Bottom Line: The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit.Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation.Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China.

ABSTRACT
The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic.

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The different proliferative ability of Z138c-TMP2 and Z138c-miRNA-17-92 cell lines after different doses of radiation. The cell proliferation of Z138c cells expressing miRNA-17-92 or control vector was detected using a 3H-TdR incorporation assay after different doses of irradiation. A) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells after different doses of radiation. B) the cell proliferation of cells without radiation. C) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells at different days after 2 Gy radiation. D) the cell proliferation of cells at different days after 4 Gy radiation. Data have been presented as mean ± s.d. (N = 5). One representative of three experiments has been shown. *P < 0.05, **P < 0.01 or ***P < 0.001 as compared among the identical groups.
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Figure 2: The different proliferative ability of Z138c-TMP2 and Z138c-miRNA-17-92 cell lines after different doses of radiation. The cell proliferation of Z138c cells expressing miRNA-17-92 or control vector was detected using a 3H-TdR incorporation assay after different doses of irradiation. A) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells after different doses of radiation. B) the cell proliferation of cells without radiation. C) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells at different days after 2 Gy radiation. D) the cell proliferation of cells at different days after 4 Gy radiation. Data have been presented as mean ± s.d. (N = 5). One representative of three experiments has been shown. *P < 0.05, **P < 0.01 or ***P < 0.001 as compared among the identical groups.

Mentions: To investigate the effect of miRNA-17-92 on the proliferating ability of tumor cells, we detected the cell proliferation of Z138c cells expressing miRNA17-92 or control vector after irradiation using a 3H-TdR incorporation assay. There were no difference between the two groups after radiation at 0 Gy (Figure 2). However, statistically significant differences were obtained at a radiation dose of 2 Gy and incubation times of 48, 72, 96, and 120 h and at a radiation dose of 4 Gy and incubation times of 24, 48 h, 72, 96, and 120 h (P < 0.05, P < 0.01 or P < 0.001, Figure 2).


MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells.

Jiang P, Rao EY, Meng N, Zhao Y, Wang JJ - Radiat Oncol (2010)

The different proliferative ability of Z138c-TMP2 and Z138c-miRNA-17-92 cell lines after different doses of radiation. The cell proliferation of Z138c cells expressing miRNA-17-92 or control vector was detected using a 3H-TdR incorporation assay after different doses of irradiation. A) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells after different doses of radiation. B) the cell proliferation of cells without radiation. C) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells at different days after 2 Gy radiation. D) the cell proliferation of cells at different days after 4 Gy radiation. Data have been presented as mean ± s.d. (N = 5). One representative of three experiments has been shown. *P < 0.05, **P < 0.01 or ***P < 0.001 as compared among the identical groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2984457&req=5

Figure 2: The different proliferative ability of Z138c-TMP2 and Z138c-miRNA-17-92 cell lines after different doses of radiation. The cell proliferation of Z138c cells expressing miRNA-17-92 or control vector was detected using a 3H-TdR incorporation assay after different doses of irradiation. A) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells after different doses of radiation. B) the cell proliferation of cells without radiation. C) the cell proliferation of Z138c-TMP2 or Z138c-miRNA-17-92 cells at different days after 2 Gy radiation. D) the cell proliferation of cells at different days after 4 Gy radiation. Data have been presented as mean ± s.d. (N = 5). One representative of three experiments has been shown. *P < 0.05, **P < 0.01 or ***P < 0.001 as compared among the identical groups.
Mentions: To investigate the effect of miRNA-17-92 on the proliferating ability of tumor cells, we detected the cell proliferation of Z138c cells expressing miRNA17-92 or control vector after irradiation using a 3H-TdR incorporation assay. There were no difference between the two groups after radiation at 0 Gy (Figure 2). However, statistically significant differences were obtained at a radiation dose of 2 Gy and incubation times of 48, 72, 96, and 120 h and at a radiation dose of 4 Gy and incubation times of 24, 48 h, 72, 96, and 120 h (P < 0.05, P < 0.01 or P < 0.001, Figure 2).

Bottom Line: The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit.Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation.Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Peking University Third Hospital, Beijing 100191, China.

ABSTRACT
The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic.

Show MeSH
Related in: MedlinePlus