B-cell non-Hodgkin lymphomas (B-NHLs) are often characterized by the development of resistance to chemotherapeutic drugs and/or relapse. During drug-induced apoptosis, Yin Yang 1 () transcription factor might modulate the expression of apoptotic regulators genes. The present study was aimed to: (1) examine the potential oncogenic role of in reversing drug resistance in B-NHLs; and (2) identify transcriptional target(s) that regulate the apoptotic pathway in B-NHLs. Predictive analyses coupled with database-deposited data suggested that binds the promoter of the /survivin anti-apoptotic gene. Gene Expression Omnibus (GEO) analyses of several B-NHL repositories revealed a conserved positive correlation between and survivin, both highly expressed, especially in aggressive B-NHLs. Further validation experiments performed in Raji Burkitt's lymphomas cells, demonstrated that silencing was associated with survivin downregulation and sensitized the cells to apoptosis. Overall, our results revealed that: (1) and survivin are positively correlated and overexpressed in B-NHLs, especially in BLs; (2) strongly binds to the survivin promoter, hence survivin may be suggested as transcriptional target; (3) silencing sensitizes Raji cells to drug-induced apoptosis via downregulation of survivin; (4) both and survivin are potential diagnostic markers and therapeutic targets for the treatment of resistant/relapsed B-NHLs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504013 | PMC |
http://dx.doi.org/10.3390/ijms21176446 | DOI Listing |
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