LncRNA & Wnt signaling in colorectal cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Javed Z
PROVIDER: S-EPMC7372757 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
LncRNA & Wnt signaling in colorectal cancer.
Javed Zeeshan Z Khan Khushbukhat K Sadia Haleema H Raza Shahid S Salehi Bahare B Sharifi-Rad Javad J Cho William C WC
Cancer cell international 20200720
The outlook for new therapeutic approaches is pivotal to ameliorate the deterioration caused by the abrogated <i>Wnt</i> signaling. Long non-coding RNAs (<i>lncRNAs</i>) are tiny molecules that have begun emerging as vital molecular manager for the regulation of various cellular processes at transcription and translation levels in the colorectal cancer (CRC). Targeting <i>Wnt</i> pathway with lncRNA seems a promising approach to eradicate CRC. However, little is known of their active role in com ...[more]
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Project description:BackgroundColorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women in China. In previous studies, Sestrin2 was demonstrated to have functions in CRC. However, the relationship between Sestrin2 and cancer stemness has not been reported.Methods and resultsTo investigate the contribution of Sestrin2 in CRC, we performed bioinformatics analysis of The Cancer Genome Atlas datasets and found that Sestrin2 was downregulated in CRC. Using a lentivirus vector, we verified that Sestrin2 suppressed CRC cell proliferation, migration, and colony formation. Furthermore, sphere formation, flow cytometry, quantitative PCR, and western blot analysis verified the influence of Sestrin2 on cancer stemness, including the expression of cluster of differentiation 44, octamer-binding transcription factor 4, sex-determining region Y-Box 2, CXC chemokine receptor 4, and the Wnt pathway downstream factors β-catenin and c-Myc. Consistently, the Wnt pathway activator BML-284 partially rescued the effects of Sestrin2 on the expression of proteins related to cancer stemness. Furthermore, in a mouse xenoplant model, tumors expressing Sestrin2 were significantly reduced in size with corresponding changes in cancer stemness.ConclusionsCollectively, our results suggest that Sestrin2 inhibits CRC cell progression by downregulating the Wnt signaling pathway. Thus, Sestrin2 may be a promising therapeutic target for CRC.
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