Revealing the role of serum exosomal novel long non-coding RNA NAMPT-AS as a promising diagnostic/prognostic biomarker in colorectal cancer patients.

AIMS: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Nicotinamide phosphoribosyl-transferase (NAMPT) was found to be over-expressed in several cancers including CRC. NAMPT-Antisense (NAMPT-AS) is a novel long non-coding RNA (lncRNA) recently reported to be associated with triple negative breast cancer. However, its role in CRC has not been investigated. This study was designed to explore the role of lncRNA NAMPT-AS in CRC, and to investigate its circulating serum exosomal levels in subjects with/without CRC. MAIN METHODS: We analyzed CRC patients' data in The Cancer Genome Atlas (TCGA). LncRNA NAMPT-AS and NAMPT mRNA levels were measured in serum exosomes isolated from CRC patients and healthy control subjects and were also measured in CRC-tissues using qRT-PCR. Serum NAMPT protein levels were measured by ELISA, and immunohistochemical analyses were done for NAMPT and Ki67 in CRC tissues. KEY FINDINGS: Serum exosomal NAMPT-AS levels were found to be significantly higher in CRC patients compared to control subjects and significantly positively correlated with serum exosomal NAMPT mRNA and circulating NAMPT protein. Tissue NAMPT-AS was found to be significantly positively associated with tissue and serum exosomal NAMPT levels. Higher serum exosomal NAMPT-AS levels were found to be associated with higher susceptibility for CRC. Gene-ontology results and survival analysis of TCGA-data showed a potential classification of CRC samples based on NAMPT-AS levels and association of NAMPT-AS upregulation with poor CRC prognosis and survival. SIGNIFICANCE: These results portray NAMPT-AS as a novel potential diagnostic/prognostic biomarker and key molecular mediator in CRC.

CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 interaction: In-silico and clinically implicated in CRC progression, correlated to tumor stage and size in case-controlled study; step toward ncRNA precision.

Unravel the regulatory mechanism of lncRNA CCDC144NL-AS1 in CRC hsa-miR-143-3p, downstream protein HMGA2 interaction arm, association with clinicopathological characteristics. Using peripheral blood as liquid biopsy from 60 CRC patients and 30 controls. The expression levels of CCDC144NL-AS1 and hsa-miR-143-3p detected by qRT-PCR. CCDC144NL-AS1 expression was significantly upregulated in CRC patients' sera, associated with worse CRC clinicopathological features regarding the depth of tumor invasion and highly significant difference between tumor stages 3 and 4 and tumor stages 2 and 4. While, hsa-miR-143-3p expression was downregulated in CRC patients by 4.5-fold change when compared to the control subjects (p < 0.0001) and HMGA2 increased in CRC patients than controls 19.59 ng/µL and 5.377 ng/µL, respectively (p < 0.0001) with significant difference between tumor stages 3 and 4 as well as tumor stages 2 and 4. CRC patients with large tumor size showed upregulation in CCDC144NL-AS1 expression and HMGA2 levels compared to those with small tumor size (p-value = 0.0365 and 0.013, respectively). CCDC144NL-AS1 and HMGA2 were positively correlated, whereas lncRNA CCDC144NL-AS1 and hsa-miR-143-3p were negatively correlated. Conclusion: As an interaction arm CCDC144NL-AS1/hsa-miR-143-3p/HMGA2 were correlated to CRC stages 2-4. Therefore, this interaction arm expression clinically and in silico approved, would direct treatment precision in the near future.