The long non-coding RNA PCA3: an update of its functions and clinical applications as a biomarker in prostate cancer

Abstract

Prostate cancer antigen 3 (PCA3) is an overexpressed prostate long non-coding RNA (lncRNA), transcribed from an intronic region at the long arm of human chromosome 9q21–22. It has been described that PCA3 modulates prostate cancer (PCa) cell survival through modulating androgen receptor (AR) signaling, besides controlling the expression of several androgen responsive and cancer-related genes, including epithelial–mesenchymal transition (EMT) markers and those regulating gene expression and cell signaling. Also, PCA3 urine levels have been successfully used as a PCa diagnostic biomarker. In this review, we have highlighted recent findings regarding PCA3, addressing its gene structure, putative applications as a biomarker, a proposed origin of this lncRNA, roles in PCa biology and expression patterns. We also updated data regarding PCA3 interactions with cancer-related miRNAs and expression in other tissues and diseases beyond the prostate. Altogether, literature data indicate aberrant expression and dysregulated activity of PCA3, suggesting PCA3 as a promising relevant target that should be even further evaluated on its applicability for PCa detection and management.

The roles of long noncoding RNAs in breast cancer metastasis

“…1). (1) Intergenic lncRNAs originate from DNA sequences between two protein-coding genes, such as MALAT1 13 , Linc-ROR 14 , and ANCR 15 ; (2) intronic lncRNAs originate from introns of protein-coding genes, such as PRUNE2 16 , PCA3 17 , COLDAIR 18 , and SYISL 19 ;…”

“…1 ). (1) Intergenic lncRNAs originate from DNA sequences between two protein-coding genes, such as MALAT1 13 , Linc-ROR 14 , and ANCR 15 ; (2) intronic lncRNAs originate from introns of protein-coding genes, such as PRUNE2 16 , PCA3 17 , COLDAIR 18 , and SYISL 19 ; (3) sense lncRNAs overlap with one or more introns and exons of different protein-coding genes, such as LncRNA-GAS5 13 and ecCEPBA 20 ; (4) antisense lncRNAs originate from an opposite direction to a protein-coding gene, such as TALAM1 21 , PDCD4-AS1 22 , and Wrap53 23 ; (5) enhancer lncRNAs originate from the regions of promoter enhancer, such as LncRNA-LEENE 24 and Lnc-SLC4A1-1 25 ; and (6) bidirectional lncRNAs exist in proximity of a coding transcript of the opposite strand, such as Linc00441 26 and Catsper1au 27 . So far, lncRNAs have been shown to exert auxiliary functions either to tumor suppression or to tumorigenesis.…”

SPLICE-q: a Python tool for genome-wide quantification of splicing efficiency

“…Although this overview suggests that there is no alteration in average splicing efficiency levels between normal and tumor tissue, a closer look showed interesting changes for individual introns. One intriguing example is Prostate cancer associated 3 (PCA3), a long noncoding RNA highly expressed in prostate cancer and widely known as a prostate cancerspecific biomarker of high specificity [29]. It has been found to be involved in the proliferation and survival of prostate cancer cells by multiple mechanisms, including the modulation of androgen receptor signaling, the inhibition of the tumor suppressor PRUNE2, and possibly by acting as a competing endogenous RNA (ceRNA) for High mobility group box 1 (HMGB1) via sponging of miR-218-5p [29–31].…”

“…One intriguing example is Prostate cancer associated 3 (PCA3), a long noncoding RNA highly expressed in prostate cancer and widely known as a prostate cancerspecific biomarker of high specificity [29]. It has been found to be involved in the proliferation and survival of prostate cancer cells by multiple mechanisms, including the modulation of androgen receptor signaling, the inhibition of the tumor suppressor PRUNE2, and possibly by acting as a competing endogenous RNA (ceRNA) for High mobility group box 1 (HMGB1) via sponging of miR-218-5p [29–31]. Interestingly, PCA3’s second intron located at chr9:76,782,833-76,783,704 has an SE of 0.57 in normal tissue and a much higher SE of 0.90 in the tumor ( Fig.…”

LncRNAs in Non-Small-Cell Lung Cancer

“…As reviewed in Shi et al, lncRNAs could be used to distinguish early-stage disease from healthy patients at a high sensitivity and specificity, as well as providing prognostic insight into the risk of metastases and recurrence [124]. For example, prostate cancer antigen 3 (PCA3) is an overexpressed lncRNA in prostate cancer (PCa) that contributes to PCa progression by modulating androgen signaling, and PCA3 urine levels were successfully used as a biomarker for PCa diagnosis [125].…”