PCAT1 (Prostate Cancer Associated Transcript 1)

PCAT1, PCAT2, and PCAT3 lncRNAs significantly increase in cervical cancerous tissues and may play a role as novel oncogenes. Their use as clinical diagnostic markers requires further studies.

Our research suggested that PCAT1, PCAT2, and PCAT5 may be engaged in promoting and developing GC cells as a novel oncogene because of the increased expression of PCAT1, PCAT2 and PCAT5 in tumor tissues of GC patients. Additionally, PCAT1, PCAT2, and PCAT5 can be thought of as poor diagnostic biomarkers for GC case detection.

LncRNA PCAT1 was overexpressed in CC cells and facilitated CC cell proliferation and invasion via inhibition of miR-128-3p and promotion of SEC61A1.

Our results revealed that the extent of induction of ARLNC1 by androgen is modulated by receptor expression status. In addition, we determined that AR blockade, via enzalutamide, effectively suppresses ARLNC1 both at baseline and after induction by DHT.

In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice. LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis.

Moreover, ZNF217 knockdown significantly decreased MTA2, MTA3, and SNAI1 expressions, but increased E-cadherin expressions in both CRC cells lines. Exosomal lncRNA PCAT1 can promote the adhesion and invasion of CRC cells, and PCAT1 overexpression may lead to ZNF217 upregulation that regulates EMT-related MTA2/MTA3/Snai1/E-cadherin signaling.

PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signalling-mediated T-cell activation. Inhibition of PCAT1 and SOX2 synergised with radiotherapy to activate the immune response and could serve as potential therapeutic targets.

Finally, transcription factor AP-2 gamma (TFAP2C) activated PCAT1 expression at the transcriptional level to reduce ferroptosis susceptibility and enhance chemoresistance. Collectively, our findings demonstrated that TFAP2C-induced PCAT1 promotes chemoresistance by blocking ferroptotic cell death through c-Myc/miR-25-3p/SLC7A11 signaling.

PCAT1/SOX2 axis promoted tumorigenesis and immunosuppression through inhibition of cGAS/STING signaling-mediated T-cell activation. Inhibition of PCAT1 and SOX2 synergized with radiotherapy to activate the immune response and could serve as potential therapeutic targets.

These suppressive effects of AR and MYC are mitigated at shared AR/MYC binding sites, which also have markedly higher levels of H3K27 acetylation, indicating enrichment for functional enhancers. These findings demonstrate an intricate balance between AR and MYC, and indicate that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy.

Lnc-PCAT1 dysregulation serves as a biomarker for diagnosis and prognosis for MM.