Samad, Muhammad Azizan and Saiman, Mohd Zuwairi and Majid, Nazia Abdul and Karsani, Saiful Anuar and Yaacob, Jamilah Syafawati (2024) Berberine and RNAi-Targeting Telomerase Reverse Transcriptase (TERT) and/or Telomerase RNA Component (TERC) Caused Oxidation in Colorectal Cancer Cell Line, HCT 116: An Integrative Approach using Molecular and Metabolomic Studies. Cell Biochemistry and Biophysics, 82 (1). pp. 153-173. ISSN 1085-9195, DOI https://doi.org/10.1007/s12013-023-01210-8.
Full text not available from this repository.Abstract
Colorectal cancer (CRC) is the most common cancer in both men and women and is associated with increased telomerase levels and activity. The potential downstream effects of TERT and/or TERC downregulation by berberine (a telomerase inhibitor) or RNA interference (RNAi) on various target RNAs, proteins, relative telomerase activity (RTA), relative telomere length (RTL), hydrogen peroxide concentration H2O2], percentage of cell cycle distribution, cell size and granularity as well as cellular metabolites were explored in HCT 116 cell line. Knockdown of TERT decreased TERC. The downregulation of TERT and/or TERC caused increment of H2O2], G(0)/G(1) phase arrest in addition to decreased S and G(2)/M phases, as well as diminished cell size. RTL was later reduced as a result of TERT, TERT and/or TERC downregulation which decreased RTA. It was discovered that xanthine oxidase (XO) was significantly and positively correlated at FDR-adjusted p value < 0.05 with RTA, TERT, TERT, TERC, and RTL. HCT 116 with decreased RTA was closely clustered in the Principal Component Analysis (PCA) indicating similarity of the metabolic profile. A total of 55 metabolites were putatively annotated in this study, potentially associated with RTA levels. The Debiased Sparse Partial Correlation (DSPC) Network revealed that RTA was directly correlated to TERT. There were 4 metabolic pathways significantly affected by low level of RTA which include (1) purine metabolism, (2) glycine, serine, and threonine metabolism, (3) glyoxylate and dicarboxylate metabolism, and (4) aminoacyl-tRNA biosynthesis. The Gene-Metabolite Interaction Network implied that reduced RTA level was related to the mechanism of oxidative stress. This study reveals the linkages between RTA to various selected RNAs, proteins, metabolites, oxidative stress mechanism and subsequently phenotypic changes in HCT 116 which is valuable to understand the intricate biological interactions and mechanism of telomerase in CRC.
| Item Type: | Article |
|---|---|
| Funders: | Universiti Malaya (RP030C-15AFR), Universiti Malaya, Malaysia |
| Uncontrolled Keywords: | Telomerase; Telomere; TERT; TERC; Metabolomics; RNA interference |
| Subjects: | Q Science > Q Science (General) Q Science > QH Natural history |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 12 Nov 2024 04:37 |
| Last Modified: | 12 Nov 2024 04:37 |
| URI: | http://eprints.um.edu.my/id/eprint/45802 |
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