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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 expression of the proteins p-Akt, PTEN and PHLPP2 in Z138c-TMP2 and Z138c-miRNA-17-92 cells after radiation. The protein expression of pAkt, PTEN and PHLPP2 in both cell lines was detected by immunoblot analysis at 1 day after radiation as described in materials and methods. One representative of three experiments has been shown.
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Figure 5: The expression of the proteins p-Akt, PTEN and PHLPP2 in Z138c-TMP2 and Z138c-miRNA-17-92 cells after radiation. The protein expression of pAkt, PTEN and PHLPP2 in both cell lines was detected by immunoblot analysis at 1 day after radiation as described in materials and methods. One representative of three experiments has been shown.

Mentions: As PTEN and PHLPP2 are the target genes of miRNA-17-92, we thus examined the protein expression of pAkt, PTEN and PHLPP2 in both cell lines by immunoblot analysis after radiation. As shown in Figure 5, compared with Z138c control cells, PTEN and PHLPP2 protein levels were reduced in Z138c-miRNA-17-92 cells after radiation. Consistently, pAkt was enhanced in Z138c-miRNA-17-92 cells after radiation.


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 expression of the proteins p-Akt, PTEN and PHLPP2 in Z138c-TMP2 and Z138c-miRNA-17-92 cells after radiation. The protein expression of pAkt, PTEN and PHLPP2 in both cell lines was detected by immunoblot analysis at 1 day after radiation as described in materials and methods. One representative of three experiments has been shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: The expression of the proteins p-Akt, PTEN and PHLPP2 in Z138c-TMP2 and Z138c-miRNA-17-92 cells after radiation. The protein expression of pAkt, PTEN and PHLPP2 in both cell lines was detected by immunoblot analysis at 1 day after radiation as described in materials and methods. One representative of three experiments has been shown.
Mentions: As PTEN and PHLPP2 are the target genes of miRNA-17-92, we thus examined the protein expression of pAkt, PTEN and PHLPP2 in both cell lines by immunoblot analysis after radiation. As shown in Figure 5, compared with Z138c control cells, PTEN and PHLPP2 protein levels were reduced in Z138c-miRNA-17-92 cells after radiation. Consistently, pAkt was enhanced in Z138c-miRNA-17-92 cells after radiation.

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