Telomerase reverse transcriptase downregulation by RNA interference modulates endoplasmic reticulum stress and mitochond
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ORIGINAL ARTICLE
Telomerase reverse transcriptase downregulation by RNA interference modulates endoplasmic reticulum stress and mitochondrial energy production Muhammad Zuhair Mohd Zain1 · Nor Hayati Ismail1,3 · Nadhirah Ahmad1 · Sarina Sulong4 · Saiful Anuar Karsani1,2 · Nazia Abdul Majid1 Received: 2 June 2020 / Accepted: 15 September 2020 / Published online: 21 September 2020 © Springer Nature B.V. 2020
Abstract Telomerase is a cancer promoting ribonucleoprotein complex and is a potential therapeutic target for cancer. In this study, the effects of telomerase downregulation on the whole cell proteome were investigated. Understanding how the effect of downregulation on the whole proteome profile will generate a greater understanding of the possible roles played by telomerase in cancer. Downregulation was achieved by RNA interference (RNAi), targeting the telomerase reverse transcriptase (TERT) subunits of telomerase. Transfection of TERT siRNA downregulates TERT gene expression and induced downregulation of telomerase activity. Investigation of the effect of silencing TERT in telomerase was further validated through proteomic analysis by performing 2-dimension electrophoresis (2DE) coupled with MALDI-TOF/TOF. 12 protein spots in HeLa cells were reported to be significantly differentially expressed with 11 of them were upregulated and 1 downregulated. Through STRING analysis, differentially expressed proteins demonstrated strong associations with endoplasmic reticulum stress marker and mitochondrial energy production marker. In conclusions, the result exhibited novel integrated proteomic response involving endoplasmic reticulum stress and mitochondrial energy production in response to the TERT downregulation in cervical cancer cells. Keywords TERT · siRNA · Proteomic · ER stress · Mitochondria
Introduction Cervical cancer remains to be a major public health issue and was rated as the fourth most prevalent cancer among women [1]. Despite the advancement in screening and therapeutic therapy, the occurrence and mortality remains high * Nazia Abdul Majid [email protected] 1
Institute of Biological Sciences, Faculty of Science, University Malaya, 50603 Kuala Lumpur, Malaysia
2
University of Malaya Centre for Proteomics Research (UMCPR), University of Malaya, 50603 Kuala Lumpur, Malaysia
3
Makmal Kesihatan Awam Kebangsaan (National Public Health Laboratory), Ministry of Health, Lot 1853, Kampung Melayu, 47000 Sungai Buloh, Selangor, Malaysia
4
Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
noting almost 570,000 cases and 311,000 deaths in 2018 alone [1, 2]. Improvement of understanding in complex cellular pathway has bring massive effort in discovering new molecular targets for therapies. This calls for the development of new strategies in targeting these molecular targets which is necessary in increasing the chance of survivability among the cervical cancer patients [2]. Telomere is a DNA rich protective structure t
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