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article · Non-coding RNA Research

Telomerase RNA component lncRNA as potential diagnostic biomarker promotes CRC cellular migration and apoptosis evasion via modulation of β-catenin protein level

202367 citationsOpen accessUniversity of Sadat City

In plain language

Long non-coding RNA telomerase RNA component, or lncRNA TERC, functions as a potential serum biomarker and tumour promoter in colorectal cancer. In an evaluation of 70 colorectal cancer patients and 35 control subjects, lncRNA TERC appeared overexpressed in patient sera, displaying high diagnostic accuracy and the ability to discriminate between different cancer stages. Complementary experiments in colorectal cancer cell lines revealed elevated lncRNA TERC expression, whilst silencing the molecule reduced beta-catenin protein levels, triggered cell cycle arrest and apoptosis, and inhibited cell migration. These findings indicate that lncRNA TERC supports colorectal cancer progression by promoting cell migration and evading programmed cell death through the modulation of beta-catenin, pointing to its dual significance as an early diagnostic marker and a key molecular driver.

Key takeaways

  • Serum lncRNA TERC is significantly overexpressed in colorectal cancer patients and provides high accuracy for diagnosis and stage discrimination.
  • Experimental silencing of lncRNA TERC in cancer cell lines triggers cell cycle arrest, prompts apoptosis, and suppresses cellular migration.
  • Inhibition of lncRNA TERC reduces beta-catenin protein levels, clarifying its role in cancer cell survival and motility.
  • The molecule demonstrates potential utility as a non-invasive biomarker for detecting early-stage colorectal cancer.

Why it matters

Colorectal cancer outcomes depend heavily on timely and precise detection. Non-invasive blood biomarkers capable of identifying early disease and separating clinical stages could improve patient management and monitoring. Furthermore, identifying the specific molecular components that enable cancer cells to avoid cell death and spread, such as the regulation of beta-catenin, clarifies the biological pathways underpinning tumour progression.

Commercialisation angle

This early-stage research could aid diagnostic kit manufacturers and clinical laboratories in designing non-invasive, serum-based screening and staging tools for colorectal cancer. Diagnostic developers could use lncRNA TERC detection to complement existing screening methods. Given that the underlying findings rely on laboratory cell models and a small patient cohort of 70 individuals, substantial assay optimisation and large-scale clinical validation remain necessary before real-world commercial use.

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Abstract

Aim: Long non-coding RNA (LncRNA) telomerase RNA component (TERC) has telomerase-dependent and independent activity in numerous cancer types. The present study purposes to demonstrate the role of lncRNA TERC as a diagnostic serum biomarker in colorectal cancer (CRC) patients and the molecular mechanism of lncRNA TERC in inducing tumor in CRC cell lines. Materials and methods: PCR array was performed to examine lncRNAs dysregulated in CRC. LncRNA TERC expression level was evaluated in 70 CRC patients and 35 control subjects using RT-qPCR. Then transfection was performed to build down-expression models of lncRNA TERC. ROC curve analysis was applied to assess the diagnostic value of serum LncRNA CRC. In addition, RT-qPCR was used to detect expression level of lncRNA TERC and β-catenin mRNA. Moreover, ELISA and Western blot were used to detect the level of β-catenin protein in sera of CRC patients and cell lines. The biological functions such as cell growth and migration of CRC cells were assessed using a wound healing assay. Cell cycle analysis and apoptosis analysis were performed using flow cytometry. Results: The lncRNA TERC is overexpressed in the sera of CRC patients with high diagnostic and stage discrimination accuracy. Furthermore, lncRNA TERC expression was upregulated in CRC cell lines and lncRNA TERC silencing induced cell arrest and apoptosis and inhibited cell migration. Furthermore, inhibition of lncRNA TERC reduces β-catenin protein levels. Conclusion: The lncRNA TERC could be considered as an early stages CRC diagnostic biomarker with a good ability to discriminate between CRC stages. lncRNA TERC induces CRC by promoting cell migration and evading apoptosis by elevating the level of β-catenin protein.

Research topics

  • Cancer-related molecular mechanisms research
  • Telomeres, Telomerase, and Senescence
  • Circular RNAs in diseases

Sustainable Development Goals

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DOI: 10.1016/j.ncrna.2023.03.004

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