Furthermore, restoring <i>miR-141</i> expression could at least partially reverse the inhibitory effect of YY1 on cell proliferation and tumor growth and on the expression of some critical c-Myc targets, such as PTEN/AKT pathway components both <i>in vitro</i> and <i>in vivo</i> We also found that YY1 expression is reduced in NPC tissues, negatively correlates with <i>miR-141</i> expression and clinical stages in NPC patients, and positively correlates with survival prognosis.
Positive rate of EBV in NPC tissues (93.5%) was remarkably higher than that in chronic nasopharyngeal inflammation tissues (21.6%). miR-BART4 was highly expressed and mRNA and protein expression of PTEN was lowly expressed in EBV positive NPC tissues compared with EBV negative NPC tissues and chronic nasopharyngeal inflammation tissues.
Our findings demonstrate that the BRD7/miR-141/PTEN/AKT axis has critical roles in the progression of NPC and provide some promising targets for the diagnosis and treatment of NPC.
Phosphatase and tensin homolog (PTEN), a tumor suppressor, was reported to be downregulated in NPC patients and correlated with pathological grade and clinical stage of NPC.
Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and have a key role in LMP1-induced CSCs in NPC.
In NPC tissue samples showing the methylation at PTEN promoter, LMP1 was highly expressed in higher methylation intensity group relative to lower intensity group, and DNA methyltransferase 3b (DNMT3b) expression was positively correlated with LMP1 expression.
On the basis of this evidence, it is believed that cancer gene therapy combining two tumor suppressors such as ING4 and PTEN can be used to establish an effective and novel therapeutic strategy for nasopharyngeal carcinoma and other cancers.
Reduced PTEN and PPP2R2B expression correlated with activated AKT/mTOR and PDK1/MYC pathways and conferred considerable BEZ235 resistance in nasopharyngeal carcinoma.
These results first reveal an epigenetic alteration, aberrant methylation of PTEN, in NPC, which is probably an early event and may be regarded as a novel candidate biomarker for early stage of NPC detection and prevention.
The present study is to investigate the role of microRNA-21 (miR-21) in nasopharyngeal carcinoma (NPC) and the mechanisms of regulation of PTEN by miR-21.
Our research group established the radioresistant NPC cell line CNE2R derived from the CNE2 cell line, and demonstrated that irradiation-induced miR-205 determined the resistance of NPC through directly targeting PTEN.
Further, we found that miR-144 was inversely correlated with the tumor suppressor gene phosphatase and tensin homolog (PTEN) in NPC specimens and cell lines, and then we identified PTEN as a direct target of miR-144 in NPC cell lines.
Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling).
Significantly, immunohistochemistry studies demonstrate that PTEN is downregulated at late stages of NPC, and that miR-205 is significantly elevated followed the radiotherapy.