Nada Mohammed El-Sheikh

Conference 2023 Live Talk

Talk title

Elevated non-coding NNT-AS1 relation to HSP90 in colorectal cancer patients: The story of negative correlation to hsa-miR-485-5p

Authors and Affiliations

Nada M. El-Sheikh1, Ahmed I. Abulsoud1, 2, Amal Fawzy3, Eman F. Wasfey4, Nadia M. Hamdy4, 5*

1. Biochemistry Department, Faculty of Pharmacy, Heliopolis University, El Salam City, 11785, Cairo, Egypt
2. Biochemistry Department, Faculty of Pharmacy (Boy’s Branch), Al-Azhar University, Nasr City, 11884, Cairo, Egypt
3. Department of Clinical and Chemical Pathology, National Cancer Institute, Cairo University, 11796, Cairo, Egypt
4. Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, 11566, Cairo, Egypt
5. The National Committee of Drugs, Academy of Scientific Research and Technology (ASRT), 11516, Cairo, Egypt

Abstract

Background

Nicotinamide nucleotide transhydrogenase-antisense 1 (NNT-AS1) is a newly-discovered long non-coding RNA (lncRNA). It has been found to be dysregulated in a variety of neoplastic diseases. However, NNT-role AS1’s in colorectal cancer (CRC) has not been well investigated.
This study aimed to assess how the NNT-AS1/homo sapiens (hsa)-microRNA (miR)-485-5p/heat shock protein 90 (HSP90) axis might regulate CRC.

Methods

Sixty Egyptians with CRC and 28 healthy controls were selected for the study, and peripheral blood liquid samples were taken from both groups. Profiles of the patients were gathered for information on demographics and clinicopathological characteristics. Levels of lncRNA NNT-AS1 and hsa-miR-485-5p expression were measured in patient serum using qRT-PCR. The protein level of HSP90 was quantified by ELISA. Serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) were determined using electrochemiluminescence immunoassay. The clinicopathological features of the patients and the relative expression levels of the investigated non-coding RNAs, as well as the HSP90 concentration, were associated with one another. In addition, receiver operating characteristic (ROC) curve analysis was used to examine the diagnostic value of the axis in comparison to standard blood-based tumor markers (TMs).

Results

In CRC Egyptian patient cohort serum, there was an upregulation in the relative expression level of lncRNA NNT-AS1 56.7 (13.5-112) and HSP90 ELISA level 6.68 (5.14–8.77); however, the relative expression level of hsa-miR-485-5p 0.0474 (0.0236-0.135) was downregulated, compared to healthy control subjects. For lncRNA NNT-AS1, it showed a specificity of 96.4% and a sensitivity of 91.7%, a specificity of 96.4% and a sensitivity of 90% was shown for hsa-miR-485-5p, and for HSP90, it revealed a specificity of 89.3% and a sensitivity of 70%. These specificities and sensitivities outperformed the classical CRC TMs, which demonstrated specificities and sensitivities of 69.7% and 68.3% for CEA and 57.1% and 55% for CA19-9, respectively. There was a substantial negative correlation between lncRNA NNT-AS1 and hsa-miR-485-5p (r= -0.933) and miRNA-485-5p and HSP90 (r= -0.997). However, a substantial positive correlation was detected between the lncRNA NNT-AS1 and HSP90 (r= 0.927).

Conclusions

When correlated with CRC histologic grades 1-3, our results imply that elevated expression of lncRNA NNT-AS1 may contribute in CRC progression via modifying the NNT-AS1/hsa-miR-485-5p/HSp90 axis in an Egyptian CRC patient’s cohort. After demonstrating its high diagnostic efficacy in comparison to the conventional blood based TMs, this may present a new opportunity for early detection of CRC and for targeted therapy for CRC treatment.