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Telomerase reverse transcriptase downregulation by RNA interference modulates endoplasmic reticulum stress and

Muhammad Zuhair Mohd Zain1, Nor Hayati Ismail1,2, Nadhirah Ahmad1

  • 1Institute of Biological Sciences, Faculty of Science, University Malaya, 50603, Kuala Lumpur, Malaysia.

Molecular Biology Reports
|September 22, 2020
PubMed

Insights

This study investigated the impact of telomerase reverse transcriptase (TERT) downregulation on the proteome of cervical cancer cells. Silencing TERT revealed integrated responses involving endoplasmic reticulum stress and mitochondrial energy production.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • Telomerase is a ribonucleoprotein complex implicated in cancer promotion.
  • Telomerase presents a potential therapeutic target for various cancers.
  • Understanding telomerase's role in cancer requires investigating its proteomic effects.

Purpose of the Study:

  • To investigate the effects of telomerase downregulation on the whole cell proteome.
  • To elucidate the potential roles of telomerase in cancer through proteomic profiling.
  • To analyze the integrated cellular response to telomerase inhibition.

Main Methods:

  • Telomerase downregulation was achieved using RNA interference (RNAi) targeting the telomerase reverse transcriptase (TERT) subunit.
  • TERT gene expression and telomerase activity were assessed following siRNA transfection.
  • Proteomic analysis was performed using 2-dimension electrophoresis (2DE) coupled with MALDI-TOF/TOF mass spectrometry.

Main Results:

  • Significant differential expression of 12 protein spots was observed in HeLa cells upon TERT silencing.
  • 11 of the differentially expressed proteins were upregulated, and 1 was downregulated.
  • STRING analysis indicated strong associations between these proteins and endoplasmic reticulum stress and mitochondrial energy production markers.

Conclusions:

  • TERT downregulation in cervical cancer cells triggers a novel integrated proteomic response.
  • This response involves significant alterations in pathways related to endoplasmic reticulum stress.
  • Mitochondrial energy production pathways are also implicated in the cellular response to TERT inhibition.
Keywords:
ER stressMitochondriaProteomicTERTsiRNA

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