Bromodomain Inhibitor JQ1 Provides Novel Insights and Perspectives in Rhabdomyosarcoma Treatment

被引：7
|
作者：
Marchesi, Irene [1 ,2 ]
Fais, Milena [1 ]
Fiorentino, Francesco Paolo [1 ,2 ]
Bordoni, Valentina [1 ]
Sanna, Luca [1 ]
Zoroddu, Stefano [1 ]
Bagella, Luigi [1 ,3 ]
机构：
[1] Univ Sassari, Dept Biomed Sci, Viale San Pietro 43-B, I-07100 Sassari, Italy
[2] Kitos Biotech Srls, I-07041 Tramariglio, Alghero, Italy
[3] Temple Univ, Coll Sci & Technol, Ctr Biotechnol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 07期
关键词：
BET inhibition; rhabdomyosarcoma; MYC; BRD4; (+)-JQ1; GROWTH SUPPRESSION; PROGNOSTIC-FACTORS; BET BROMODOMAINS; UNITED-STATES; CELL-LINES; RESISTANCE; MYC; ENHANCER; PROLIFERATION; CHILDHOOD;
D O I：
10.3390/ijms23073581
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Rhabdomyosarcoma (RMS) is the most common type of pediatric soft tissue sarcoma. It is classified into two main subtypes: embryonal (eRMS) and alveolar (aRMS). MYC family proteins are frequently highly expressed in RMS tumors, with the highest levels correlated with poor prognosis. A pharmacological approach to inhibit MYC in cancer cells is represented by Bromodomain and Extra-Terminal motif (BET) protein inhibitors. In this paper, we evaluated the effects of BET inhibitor (+)-JQ1 (JQ1) on the viability of aRMS and eRMS cells. Interestingly, we found that the drug sensitivity of RMS cell lines to JQ1 was directly proportional to the expression of MYC. JQ1 induces G1 arrest in cells with the highest steady-state levels of MYC, whereas apoptosis is associated with MYC downregulation. These findings suggest BET inhibition as an effective strategy for the treatment of RMS alone or in combination with other drugs.
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页数：13
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