Long Noncoding RNAs CAT2064 and CAT2042 may Function as Diagnostic Biomarkers for Prostate Cancer by Affecting Target MicrorRNAs

Abstract

Prostate cancer (PCa) is the second most common cancer in men throughout the world, and the main cause of cancer death. Long noncoding RNAs (lncRNAs) act as crucial regulators in many human cancers. In this research, we measured the expression level of novel lncRNAs and their associated micro-RNAs (miRNAs) in PCa. In the present research, three lncRNAs were selected using the Mitranscriptome projec (CAT2064, CAT2042, and CAT2164.2). Samples of prostate tissue (20 PCa, and 20 BPH) and blood (14 PCa, and 14 BPH) were collected and the Real-time Quantitative Polymerase Chain Reaction (RT-qPCR) was used to measure the expression levels of the lncRNAs and their associated miRNAs. Based on our results, CAT2064 was significantly increased and CAT2042 was significantly decreased in human PCa tissue in comparison with BPH tissue. To discriminate PCa from BPH, CAT2064 (P < 0.05; 0.8750 AUC-ROC) showed a better potential as a diagnostic molecular biomarker compared to CAT2042 (P < 0.05; 0.8454 AUC-ROC). Furthermore, RT-qPCR results measured in blood samples from PCa patients showed a higher expression level of CAT2064 (P < 0.0001; AUC-ROC value of 0.8914) in comparison to CAT2042. CAT2064 and CAT2042 showed a positive correlation with the expression of miR-5095 and miR-1273a (r = 0.02885, 0.3202; P = 0.9413, 0.2266, respectively). CAT2064 and CAT2042 also had a negative correlation with miR-1304-3p and miR-1285-5p (r = - 0.3877, - 0.09330; P = 0.15, 0.7311, respectively). Collectively, CAT2064 and CAT2042 and their miRNA targets may constitute a regulatory network in PCa, and could serve as novel biomarkers.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-021-00999-6.

Keywords: BPH; Biomarker; PCa; lncRNA; miRNA.

Fig. 1

Bioinformatics studies. a Up-regulation of CAT2064 in PCa versus normal samples. b and c down-regulation of CAT2042 and CAT2164.2 in PCa versus normal samples based on Mitranscriptome project (Color Code: Cancer (Left); Normal (Right))

Fig. 2

CAT2064 lncRNA as a PCa biomarker. a Schematic representation of the chromosomal location of CAT2064 lncRNA b RT-PCR analysis of CAT2064 expression in PC3 and LNCaP cell lines. c Relative gene expression of CAT2064 in PCa and BPH samples. The gene expression was normalized with the β-actin reference gene, and obtained by the 2^−ΔΔCt method. d ROC curve analysis showing the sensitivity and specificity of CAT2064 for diagnosis of the PCa in tissue specimens AUC = 0.8750 (95%CI: 0.7553–0.9947). All data are represented as mean ± SD

Fig. 3

CAT2042 lncRNA as a PCa biomarker. a Schematic representation of the chromosomal location of CAT2042 lncRNA b RT-PCR analysis of CAT2042 expression in PC3 and LNCaP cell lines. c Relative gene expression of CAT2042 in tumor and BPH samples. The gene expression was normalized with the β-actin reference gene, and obtained by 2^−ΔΔCt method. d ROC Curve analysis showing that CAT2042 had an AUC = 0.8454 (95%CI: 0.7144–0.9764) in PCa tissue samples. All data are represented as mean ± SD

Fig. 4

Expression of target miRNAs. a Differential expression of hsa-miR-1304-3p, hsa-miR-5095, hsa-miR-1285-5p and hsa-miR-1273a in tumor and BPH samples. b The expression of CAT2064 in blood samples of PCa patients. Its expression was quantified by real-time PCR in 14 BPH and 14 PCa blood samples, β-actin was used as the reference gene. All data are represented as mean ± SD. c ROC curve analysis showing the sensitivity and specificity of the CAT2064 as a biomarker in blood samples (AUC = 0.8914; 95% CI: 0.7805 to 1.000)

Fig. 5

Correlation of gene expression. a Negative correlation (r = − 0.1170) between CAT2064 and CAT2042 expression. b Negative correlation between CAT2064 and hsa-miR-1304-3p (r = − 0.3877) c. Positive correlation between CAT2064 and hsa-miR-5095 (r = 0.02885). d Negative correlation between CAT2042 and hsa-miR-1285-5p (r = − 0.09330). e Positive correlation between CAT2042 and hsa-miR-1273a (r = 0.3202)

Fig. 6

Schematic diagram representing the involvement of lncRNAs and their targeted miRNAs in prostate cancer