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

ABSTRACT: 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.

SUBMITTER: Bardhan A

PROVIDER: S-EPMC8561087 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Triple-negative breast cancer (TNBC) is a malignant subtype of breast cancer with the absence of targeted therapy, resulting in poor prognosis in patients. Chemotherapy remains the mainstay of treatment for TNBC; however, development of drug resistance is the main obstacle for successful treatments. In recent years, long non-coding RNA (lncRNA) has been implicated in multiple biological functions in various diseases, particularly cancers. Accumulating evidence suggested that lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) expression is dysregulated in many human cancers and thus is a useful prognostic marker for cancer patients. Nevertheless, the mechanism of how NEAT1 confers drug resistance in TNBC is still largely unknown. We performed lncRNA profiling by the LncRNA Profiler qPCR Array Kit in normal control (NC) and breast cancers (BC) blood samples and further validated in a larger cohort of samples by qRT-PCR. Gene expression level and localization were investigated by qRT-PCR, western blotting, and immunofluorescence staining. Flow cytometric analysis was carried out to detect cancer stem cells. Functional studies were performed both in vitro and in vivo xenograft model. Among 90 lncRNAs, NEAT1 was highly expressed in the blood samples of breast cancer patients than in NC. In particular, the expression of NEAT1 was higher in TNBC tissues than other subgroups. Functional studies revealed that NEAT1 conferred oncogenic role by regulating apoptosis and cell cycle progression in TNBC cells. We identified that knockdown of NEAT1 sensitized cells to chemotherapy, indicating the involvement in chemoresistance. Importantly, shNEAT1 reduced stem cell populations such as CD44+/CD24-, ALDH+, and SOX2+, implicating that NEAT1 was closely related to cancer stemness in TNBC. Our data highlighted the roles of NEAT1 chemoresistance and cancer stemness, suggesting that it could be used as a new clinical therapeutic target for treating TNBC patients especially those with drug resistance.

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

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