LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis in-silico and clinical prospect correlated-to histologic grades-based CRC stratification: A step toward ncRNA Precision

The oncogenic effects of long non-coding RNA (lncRNA) Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) role in colorectal cancer (CRC) hasn't been sufficiently inspected in relation to the Homo sapiens (hsa)-microRNA (miR)-485-5p/ heat shock protein 90 (HSP90) axis, clinically. qRT-PCR was per-formed to detect lncRNA NNT-AS1 and hsa-miR-485-5p expression levels in 60 Egyptian patients' sera. HSP90 serum level was quantified using Enzyme-linked immunosorbent assay (ELISA). The relative expression level of the studied non-coding RNAs as well as the HSP90 ELISA concentration were correlated with patients clinico-pathological characteristics and correlated to each other. The axis diagnostic utility in comparison with carbo-hydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) tumor markers (TMs) was studied by receiver operating characteristic (ROC) curve analysis. The relative lncRNA NNT-AS1 expression level fold change 56.7 (13.5-112) and HSP90 protein ELISA level 6.68 (5.14-8.77) (ng/mL) were elevated, while, for hsa-miR-485-5p 0.0474 (0.0236-0.135) expression fold change was repressed in CRC Egyptian patients' cohort sera, being compared to 28 apparently healthy control subjects. LncRNA NNT-AS1 specificity is 96.4% and a sensi-tivity of 91.7%, hsa-miR-485-5p showed 96.4% specificity, 90% sensitivity, and for HSP90 89.3%, 70% speci-ficity and sensitivity, respectively. Those specificities and sensitivities were superior to the classical CRC TMs. A significant negative correlation was found between hsa-miR-485-5p with lncRNA NNT-AS1 (r =-0.933) expression fold change or with HSP90 protein blood level (r =-0.997), but, significant positive correlation was there between lncRNA NNT-AS1 and HSP90 (r = 0.927). LncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis could be a prospect for CRC development as well as diagnosis. Being correlated and related to CRC histologic grades 1-3, therefore, lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis (not individually) expression approved clinically and in silico, could aid treatment precision.

Automated summary

This study investigated the role of long non-coding RNA (lncRNA) Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) in colorectal cancer (CRC) in relation to the Homo sapiens (hsa)-microRNA (miR)-485-5p/ heat shock protein 90 (HSP90) axis. The expression levels of lncRNA NNT-AS1, hsa-miR-485-5p, and HSP90 were examined in the sera of 60 Egyptian CRC patients. The results showed that lncRNA NNT-AS1 and HSP90 were upregulated, while hsa-miR-485-5p was downregulated in CRC patients compared to healthy controls. The findings suggest that the lncRNA NNT-AS1/hsa-miR-485-5p/HSP90 axis may be involved in CRC development and could be used for diagnosis.