Post-transcriptional Gene Regulation by MicroRNA-194 Promotes Neuroendocrine Transdifferentiation in Prostate Cancer

[snoraste]

"Summary

Potent therapeutic inhibition of the androgen receptor (AR) in prostate adenocarcinoma can lead to the emergence of neuroendocrine prostate cancer (NEPC), a phenomenon associated with enhanced cell plasticity. Here, we show that microRNA-194 (miR-194) is a regulator of epithelial-neuroendocrine transdifferentiation. In clinical prostate cancer samples, miR-194 expression and activity were elevated in NEPC and inversely correlated with AR signaling. miR-194 facilitated the emergence of neuroendocrine features in prostate cancer cells, a process mediated by its ability to directly target a suite of genes involved in cell plasticity. One such target was FOXA1, which encodes a transcription factor with a vital role in maintaining the prostate epithelial lineage. Importantly, a miR-194 inhibitor blocked epithelial-neuroendocrine transdifferentiation and inhibited the growth of cell lines and patient-derived organoids possessing neuroendocrine features. Overall, our study reveals a post-transcriptional mechanism regulating the plasticity of prostate cancer cells and provides a rationale for targeting miR-194 in NEPC."

Probably old news, but just in case.

cell.com/cell-reports/fullt...

[LearnAll]

snoraste..Nice to see you bringing this issue again on forefront. Last year when I wrote about treatment induced Neuro endocrine prostate cancer...I was furiously attacked by many members including Tall Allen. See my thread "when cure becomes worse than disease"

(LINK BELOW)

This issue of treatment emergent NE differentiation was suppressed by the Onco Complex and big pharma because they wanted to sell Zytiga, Extandi and other newer lutamides to EVERY patient whether some one needed or not.

So their philosophy became " every ones cancer is aggressive" and everyone needs aggressive treatment continuously.

Now ..more and more research is coming out saying if you suppress Androgen too strongly for too long continuously...approx, 30% of PCa will change into treatment induced Neuro endocrine which is an aggressive variant and very hard to treat.

Therefore, some honest and well respected Oncologists like Charles Myers, Laurence Klotz, Morote , Mark Sholtz dared to advocate for Intermittent Androgen Therapy in many patients who met the criteria. Intermittent ADT reduces the conversion of Andorgen dependent cancer cells into androgen Independent and Neuro Endocrine type.

Hence, I have been on Intermittent ADT for last one year

.healthunlocked.com/advanced......