Prostate Cancer-associated Non-coding RNA Research Articles

GENETIC VARIABILITY IN THE PRNCR1 GENE AMONG A SAMPLE OF IRAQI PROSTATE CANCER PATIENTS

The PRNCR1 gene variant among sample of Prostate Cancer (PCa) Iraqi patients case-control study was used, with PCa patients (n=32) and healthy individual control (n=33). It was successfully identified two SNPs in prostate cancer-associated noncoding RNA-1 (PRNCR-1) gene by using PCR technique and direct sequencing . The first SNP is rs13252298 (A>G) have three genotypes (AA,AG,GG )and the second SNP is rs5013678 (T> C) have three genotypes TT,TC,CC),these genotype frequencies were not in agreement with Hardy-Weinberg Equilibrium (HWE) in patients and controls .It was observed that AG genotype was more frequent in patients than controls(68.7% vs. 36.4%) with significant difference p<0.01 ,and the estimated OR of such a difference was 3.85 , this value was positive associated with PCa patients that mean this genotype AG was risk factor for PCa patients, it was also noticed that G allele in PCa patients compared with controls(40.6 vs.33.3%) show not significant difference p>0.05 . It was revealed that G allele have OR=1.16 that mean this allele have positive risk factor for PCa patients . In conclusion AG genotype for SNP rs13252298 was associated with PCa patients.

PRNCR1: a long non-coding RNA with a pivotal oncogenic role in cancer.

Long non-coding RNAs (lncRNAs) have been gaining importance in the field of cancer research in recent years. PRNCR1 (prostate cancer-associated non-coding RNA1) is a 12.7 kb, intron-less lncRNA found to play an oncogenic role in malignancy of diverse organs including prostate, breast, lung, oral cavity, colon and rectum. Single-nucleotide polymorphisms (SNPs) of PRNCR1 locus have been found to be associated with cancer susceptibility in different populations. In this review, an attempt has been made for the first time to summarize all sorts of available data on PRNCR1 to date from relevant databases (GeneCard, LncExpDB, Ensembl genome browser, and PubMed). As functional roles of PRNCR1, miRNA (microRNA) sponging was mostly highlighted in the pathogenesis of different cancer; in addition, an association of the lncRNA with chromatin-modifying complex to enhance androgen receptor-mediated gene transcription was reported in prostate cancer. Diagnostic and prognostic importance of PRNCR1 was found in some malignancies suggesting potency of the lncRNA to serve as a clinical biomarker. For PRNCR1 SNPs, although cancer susceptibility of the risk alleles/genotypes was reported in different populations, majorities of the findings were not replicated and underlying molecular mechanisms remained unexplored. Therapeutic implication of PRNCR1 was not studied well and future research may come up in this direction for intervening novel strategies to fight against cancer.

The Variant Allele Frequency of the lncRNA Prostate Cancer-Associated Noncoding RNA 1 (PRNCR1) rs1456315 C/T Polymorphism in Saudi Population and Colorectal Cancer Risk

ingle-nucleotide polymorphisms (SNPs) in long noncoding RNA (lncRNA) genes are associated with the onset and progression of multiple cancers in humans. These SNPs are potential biomarkers for predicting cancer risk. The variable frequency of the lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) rs1456315 C/T polymorphism may affect different ethnic groups differently, however, the information lacks for the Saudi population. The aim of this study was to assess the allelic distribution and frequency of the PRNCR1 rs1456315 C/T polymorphism in the Saudi Arabian population, as well as compare it to other populations around the world. PUBMED (Medline) and other related web-databases were referred to extract data from epidemiological studies performed in different ethnic groups. The frequency of PRNCR1 rs1456315 variant allele (C) was found to be 34.62% and a significantly different frequency was observed for the USA (p=0.01), Iran (p < /em><0.007) and China (p=0.01) ethnicity, when the Saudi occurrence is compared to those populations. Present results reveal a distinct pattern of lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) rs1456315 polymorphism variant allele in the Saudi Arabian population, which may be due to ethnic differences. The findings could assist in the risk assessment of people harbouring risk allele of rs1456315 SNP and their subsequent cancer susceptibility.

Genetic Polymorphisms of PRNCR1 and Lung Cancer Risk in Chinese Northeast Population: A Case-Control Study and Meta-Analysis.

Long noncoding RNAs (lncRNAs) play vital roles in development and progression of various cancers. To investigate the relationship between three tag single-nucleotide polymorphisms (SNPs) (rs13252298, rs1016343, and rs1456315) in lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) and lung cancer (LC) risk, we conducted this study. First, we performed a case-control study, including 576 LC patients and 612 cancer-free controls. Second, a meta-analysis was used to evaluate the association of selected SNPs with risk of overall cancer. We found that rs13252298 and rs1456315 were strongly correlated with risk of LC, nonsmall cell lung cancer (NSCLC), and lung adenocarcinoma. For rs13252298, individuals carrying GG genotype had increased risks of LC compared with those carrying AA genotype (adjusted odds ratio [OR] = 1.565, 95% CI = 1.091-2.245, p = 0.015). A significant result was also found in recessive model with adjusted OR of 1.719. Individuals with GG genotype of rs1456315 were at increased risks of LC compared with those carrying AA genotype. Similar results were found in NSCLC patients. Meta-analysis showed that rs1016343 and rs13252298 were associated with overall cancer. But for rs1016343, no significant association was observed in Asians. In conclusion, rs13252298 and rs1456315 in PRNCR1 may be genetic susceptibility factors for LC in Chinese population. These results need to be confirmed by further studies.

Long non‑coding RNA PRNCR1 exerts oncogenic effects intongue squamous cell carcinoma invitro and invivo by sponging microRNA‑944 and thereby increasing HOXB5expression.

A long non-coding RNA (lncRNA) called prostate cancer-associated non-coding RNA 1 (PRNCR1) serves crucial roles in the aggressive phenotypes of colorectal cancer and non-small cell lung cancer. However, there is little research on the expression profile, clinical value and detailed functions of PRNCR1 in tongue squamous cell carcinoma (TSCC). The aim of the present study was to determine PRNCR1 expression in TSCC and to examine the involvement of PRNCR1 in TSCC progression. The molecular mechanisms behind the oncogenic effects of PRNCR1 in TSCC cells were also investigated. PRNCR1 was revealed to be upregulated in TSCC tumors and cell lines. The high PRNCR1 expression showed a significant correlation with tumor size, clinical stage, lymph node metastasis, and shorter overall survival times among patients with TSCC. A PRNCR1-knockdown reduced TSCC cell proliferation, migration and invasion, and increased apoptosis in vitro. Additionally, the PRNCR1-knockdown slowed down in vivo tumor growth of TSCC cells. With regards to the mechanism, PRNCR1 acted as a competing endogenous RNA on microRNA-944 (miR-944) in TSCC cells, and the effects of the PRNCR1-knockdown were reversed by an miR-944-knockdown. HOXB5 was validated as a direct target gene of miR-944 in TSCC cells, and HOXB5 expression was found to be positively regulated by PRNCR1. Furthermore, resumption of HOXB5 expression reversed the tumor-suppressive actions of miR-944 in TSCC cells. In conclusion, PRNCR1 acts as an oncogenic lncRNA in TSCC through the upregulation of HOXB5 by sponging miR-944, thereby indicating a potential therapeutic target in TSCC.

Long non-coding RNA PRNCR1 has an oncogenic role in breast cancer.

Long non-coding RNAs (lncRNAs) have important roles in the development and progression of various types of human cancer. However, the expression and function of the lncRNA prostate cancer-associated non-coding RNA 1 (PRNCR1) in breast cancer remains unclear. Reverse transcription-quantitative PCR was performed to measure the levels of mRNA expression. Cell counting kit-8, flow cytometry, wound healing and Transwell assays were also performed to study cell proliferation, cell cycle, migration and invasion, respectively. The results of the present study revealed that PRNCR1 expression levels were higher in breast cancer tissues compared with adjacent normal tissues in a patient study. It was also determined that high expression of PRNCR1 was significantly associated with advanced clinical stage, positive metastasis and poor prognosis for patients with breast cancer. In vitro experiments determined that PRNCR1 was significantly upregulated in the breast cancer cell lines BT-549, MCF-7, SK-BR-3 and MDA-MB-231 compared with the normal human breast cell line, MCF-10A. Silencing of PRNCR1 significantly inhibited the proliferation, colony formation, cell cycle progression, migration and invasion of SK-BR-3 and BT-549 cells, while cell apoptosis was induced. In addition, knockdown of PRNCR1 suppressed epithelial-mesenchymal transition in SK-BR-3 and BT-549 cells. In summary, the present results demonstrated that lncRNA PRNCR1 was significantly upregulated in breast cancer and was associated with cancer progression and poor patient prognosis. In vitro experiments determined that knockdown of PRNCR1 inhibited the malignant phenotypes of breast cancer cells. Taken together, the results indicated that PRNCR1 may be used as a potential therapeutic target for patients with breast cancer.

The novel long non‑coding RNA PRNCR1‑2 is involved in breast cancer cell proliferation, migration, invasion and cell cycle progression.

Long non‑coding RNAs (lncRNAs) have recently been reported to act as important mediators of tumor initiation and progression. The present study aimed to investigate the expression and pathogenic roles of the lncRNA prostate cancer‑associated non‑coding RNA (PRNCR)1‑2 in breast cancer. The expression levels of PRNCR1‑2 were detected in breast cancer tissues and numerous breast cancer cell lines using reverse transcription‑quantitative polymerase chain reaction. Depletion of PRNCR1‑2 expression in breast cancer cells was conducted through small interfering RNA‑mediated silencing. Subsequently, cell proliferation was assessed by MTS assay, cell migration and invasion capacities were evaluated using the Transwell culture system, and cell cycle progression and apoptosis were analyzed by flow cytometry. Protein expression levels of the signaling components checkpoint kinase2 (CHK2), protein kinaseB (AKT), phosphorylated (p)‑CHK2 and p‑AKT were measured by western blotting. The results demonstrated that PRNCR1‑2 expression was significantly elevated in breast cancer tissues compared with in adjacent normal tissues. Furthermore, depletion of PRNCR1‑2 in HS‑578T and MDA‑MB‑231 breast cancer cells markedly suppressed their proliferation rates, migration and invasion capacities, and cell cycle progression; however, it had no effect on cell apoptosis. In addition, PRNCR1‑2 depletion increased CHK2 phosphorylation and decreased AKT phosphorylation in HS‑578T and MDA‑MB‑231 cells. In conclusion, the lncRNA PRNCR1‑2 may promote breast cancer cell proliferation, migration, invasion and cell cycle progression.

The expression and significance of serum PCAT-1 of colorectal cancer patients

Objective To analyze the auxiliary diagnostic value of prostate cancer-associated non-coding RNA transcript1(PCAT-1) in serum of colorectal cancer(CRC) patients. Methods The serum samples were collected from 73 patients with CRC who underwent surgical treatment and were diagnosed by pathology, 54 patients with colorectal polyps and 62 healthy controls at the Affiliated Hospital of Nantong University from October 2015 to January 2017. The serum level of PCAT-1 in CRC patients, colorectal polyps and healthy controls were measured by quantitative real-time polymerase chain reaction, respectively. The relationship between the level of PCAT-1 and the clinical pathologic feature was analyzed. Receiver operating characteristic curve(ROC) was used to evaluate the diagnosis value of PCAT-1, carcinoembryonic antigen(CEA), carbohydrate antigen 199 (CA199) alone and the combination of one of them in CRC. Results The relative expression of PCAT-1 was 2.190 0(0.852 5, 6.715 0), 0.586 5(0.331 8, 1.697 0), 0.530 0(0.127 5, 0.957 5) respectively in CRC patients, colorectal polyps and healthy controls. The expression level of serum PCAT-1 in CRC patients was not related to the age (U=593, P=0.753 3), sex (U=536, P=0.390 8), tumor size (U=549, P=0.557 2) and location (U=584, P=0.426 7), but there was related to the degree of tumor differentiation (U=30, P=0.038 4) and tumor staging (U=399, P=0.005 0). ROC curve was used to analyze the expression of serum PCAT-1, CEA and CA199 for the diagnostic efficiency of CRC. The area under the curve(AUC) of ROC were 0.836, 0.756, 0.493 respectively in comparing CRC patients with healthy controls. The sensitivity of three joint tests was 93.2%(68/73), which was higher than that of single index. The area under the curve of ROC were 0.739, 0.673, and 0.515 respectively in comparing CRC patients with colorectal polyps. The sensitivity of three joint tests was 95.9%(70/73), which was higher than that of single index. Conclusions PCAT-1 maybe has auxiliary diagnosis of CRC. The combination of PCAT-1, CEA and CA199 remarkably improved the diagnostic efficacy of CRC.(Chin J Lab Med, 2018, 41: 514-518) Key words: Colorectal neoplasms; RNA, Long noncoding; Reverse transcriptase polymerase chain reaction

Association between genetic polymorphisms of long non-coding RNA PRNCR1 and prostate cancer risk in a sample of the Iranian population.

The aim of the present study was to determine whether there is an association between the long non-coding RNA (lncRNA) prostate cancer-associated non-coding RNA 1 (PRNCR1) polymorphisms and prostate cancer (PCa) risk in a sample of the Iranian population. This case-control study was performed on 178 patients with PCa and 180 subjects with benign prostatic hyperplasia (BPH). Genotyping assay was performed by polymerase chain reaction-restriction fragment length polymorphism. The findings indicated that the GG genotype of the rs13252298 A>G variant significantly increased the risk of PCa (odds ratio=3.49, 95% confidence interval: 1.79-6.81, P=0.0001) compared with AA+AG. As regards the rs1456315 G>A polymorphism, the AG genotype and G allele significantly increased the risk of PCa. As regards the rs7841060 T>G variant, the findings demonstrated that this TG genotype and the G allele significantly increased the risk of PCa. The rs7007694 T>C variant was not found to be associated with the risk of PCa. Haplotype analysis indicated that GTGA and GTGG significantly increased the risk of PCa compared with rs1456315A/rs7007694T/rs7841060T/rs13252298G (ATTG). The PRNCR1 variants were not found to be significantly associated with the clinicopathological characteristics of PCa patients. In conclusion, our findings support an association between PRNCR1 variants and the risk of PCa in a sample of the Iranian population.

Roles of Long Non-Coding RNAs on Tumorigenesis and Glioma Development.

More than 98% of eukaryotic transcriptomes are composed of non-coding RNAs with no functional protein-coding capacity. Those transcripts also include tens of thousands of long non-coding RNAs (lncRNAs) which are emerging as key elements of cellular homeostasis, essentially tumorigenesis steps. However, we are only beginning to understand the nature and extent of the involvement of lncRNAs on tumorigeneis. Here, we highlight recent progresses that have identified a myriad of molecular functions on tumorigenesis for several lncRNAs including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), prostate cancer associated non-coding RNA 1 (PRNCR1), prostate cancer gene expression marker 1 (PCGEM1), H19, and homeobox transcript antisense intergenic RNA (HOTAIR), and several new lncRNAs for glioma development. Potential therapeutic approaches for the lncRNAs in various human diseases are also discussed.

Regulation of Apoptosis by a Prostate-Specific and Prostate Cancer-Associated Noncoding Gene, PCGEM1

PCGEM1 is a prostate tissue-specific, and prostate cancer-associated noncoding RNA (ncRNA) gene. Previous results revealed a significant association of elevated PCGEM1 expression levels in prostate cancer cells of African-American patients, whose mortality rate is the highest among prostate cancer patients. Functional study of PCGEM1 demonstrated a marked increase in colony formation in LNCaP prostate cancer cells and NIH3T3 mouse fibroblast cells. This study demonstrates that PCGEM1 overexpression in LNCaP cell culture model results in the inhibition of apoptosis induced by doxorubicin (DOX). Induction of p53 and p21(Waf1/Cip1) by DOX were delayed in LNCaP cells stably overexpressing PCGEM1 (LNCaP-PCGEM1 cells) compared to control LNCaP cells. The protein levels of cleaved caspase 7, and cleaved PARP were attenuated in DOXtreated LNCaP-PCGEM1 cells compared to control LNCaP cells. Similar results were observed in LNCaP cells transiently overexpressing PCGEM1. The inhibition of PARP cleavage by PCGEM1 overexpression was also observed in LNCaP-PCGEM1 cells incubated with etoposide and sodium selenite. Fluorescence-Activated Cell Sorter Annexin-V analysis revealed significantly lower percentage of apoptotic cells in DOX-treated LNCaP-PCGEM1 cells compared to control LNCaP cells. The attenuation of apoptic response appears to be androgen dependent in this experimental model, as androgen-independent variants of LNCaP cells did not exhibit this response. In summary, this study provides new insights into cell biologic functions and novel features of an ncRNA. Further, these data unravel biological mechanisms of cell growth/cell survival-associated functions of this ncRNA in a widely used prostate cancer cell culture model.