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

被引:55
作者
Bakr, Mohamed [1 ]
Abd-Elmawla, Mai A. [2 ]
Elimam, Hanan [1 ,3 ]
El-Din, Hebatallah Gamal [4 ]
Fawzy, Amal [5 ]
Abulsoud, Ahmed I. [6 ,7 ]
Rizk, Sherine M. [2 ]
机构
[1] Univ Sadat City, Fac Pharm, Dept Biochem, Sadat City, Egypt
[2] Cairo Univ, Fac Pharm, Dept Biochem, Cairo, Egypt
[3] Sinai Univ, Fac Pharm, Dept Biochem, Kantara, Egypt
[4] Cairo Univ, NCI, Dept Surg Oncol, Cairo, Egypt
[5] Cairo Univ, NCI, Dept Clin & Chem Pathol, Cairo, Egypt
[6] Al Azhar Univ, Fac Pharm Boys, Dept Biochem, Cairo, Egypt
[7] Heliopolis Univ, Fac Pharm, Dept Biochem, Cairo, Egypt
来源
NON-CODING RNA RESEARCH | 2023年 / 8卷 / 03期
关键词
Colorectal cancer; LncRNAs; TERC; Diagnostic biomarkers; Apoptosis evading; -catenin protein; LONG NONCODING RNA; MALIGNANT GLIOMA; CANCER; MOUSE; CELLS; OVEREXPRESSION; INHIBITION; SENESCENCE; THERAPY; MYC;
D O I
10.1016/j.ncrna.2023.03.004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 beta-catenin mRNA. Moreover, ELISA and Western blot were used to detect the level of beta-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 beta-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 beta-catenin protein.
引用
收藏
页码:302 / 314
页数:13
相关论文
共 57 条
[1]   Global patterns and trends in colorectal cancer incidence and mortality [J].
Arnold, Melina ;
Sierra, Monica S. ;
Laversanne, Mathieu ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin ;
Bray, Freddie .
GUT, 2017, 66 (04) :683-691
[2]   MYC drives overexpression of telomerase RNA (hTR/TERC) in prostate cancer [J].
Baena-Del Valle, Javier A. ;
Zheng, Qizhi ;
Esopi, David M. ;
Rubenstein, Michael ;
Hubbard, Gretchen K. ;
Moncaliano, Maria C. ;
Hruszkewycz, Andrew ;
Vaghasia, Ajay ;
Yegnasubramanian, Srinivasan ;
Wheelan, Sarah J. ;
Meeker, Alan K. ;
Heaphy, Christopher M. ;
Graham, Mindy K. ;
De Marzo, Angelo M. .
JOURNAL OF PATHOLOGY, 2018, 244 (01) :11-24
[3]   Long Noncoding RNA and Cancer: A New Paradigm [J].
Bhan, Arunoday ;
Soleimani, Milad ;
Mandal, Subhrangsu S. .
CANCER RESEARCH, 2017, 77 (15) :3965-3981
[4]   Telomere shortening and tumor formation by mouse cells lacking telomerase RNA [J].
Blasco, MA ;
Lee, HW ;
Hande, MP ;
Samper, E ;
Lansdorp, PM ;
DePinho, RA ;
Greider, CW .
CELL, 1997, 91 (01) :25-34
[5]   Long Noncoding RNAs as Biomarkers in Cancer [J].
Bolha, Luka ;
Ravnik-Glavac, Metka ;
Glavac, Damjan .
DISEASE MARKERS, 2017, 2017
[6]   LNCcation: lncRNA localization and function [J].
Bridges, Mary Catherine ;
Daulagala, Amanda C. ;
Kourtidis, Antonis .
JOURNAL OF CELL BIOLOGY, 2021, 220 (02)
[7]   Telomerase Inhibition Effectively Targets Mouse and Human AML Stem Cells and Delays Relapse following Chemotherapy [J].
Bruedigam, Claudia ;
Bagger, Frederik O. ;
Heidel, Florian H. ;
Kuhn, Catherine Paine ;
Guignes, Solene ;
Song, Axia ;
Austin, Rebecca ;
Vu, Therese ;
Lee, Erwin ;
Riyat, Sarbjit ;
Moore, Andrew S. ;
Lock, Richard B. ;
Bullinger, Lars ;
Hill, Geoffrey R. ;
Armstrong, Scott A. ;
Williams, David A. ;
Lane, Steven W. .
CELL STEM CELL, 2014, 15 (06) :775-790
[8]  
Chen C., 2022, J IMMUNOL RES, V2022
[9]   Computational models for lncRNA function prediction and functional similarity calculation [J].
Chen, Xing ;
Sun, Ya-Zhou ;
Guan, Na-Na ;
Qu, Jia ;
Huang, Zhi-An ;
Zhu, Ze-Xuan ;
Li, Jian-Qiang .
BRIEFINGS IN FUNCTIONAL GENOMICS, 2019, 18 (01) :58-82
[10]   Identification of dysregulated lncRNAs profiling and metastasis-associated lncRNAs in colorectal cancer by genome-wide analysis [J].
Chen, Yan ;
Yu, Xiang ;
Xu, Yongcan ;
Shen, Hua .
CANCER MEDICINE, 2017, 6 (10) :2321-2330