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Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer

GANG LIU1,#, LEI SHI1,#, BIN WANG1, ZEHUI WU1, HAIYUAN ZHAO1, TIANYU ZHAO2, LIANGHUI SHI1,*

1 Department of Gastrointestinal Surgery, First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, China
2 Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China

* Corresponding Author: LIANGHUI SHI. Email: email

(This article belongs to this Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2024, 32(3), 585-596. https://doi.org/10.32604/or.2023.029349

Abstract

The role of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in colon cancer involves various tumorigenic processes and has been studied widely. However, the mechanism by which it promotes colon cancer remains unclear. Retroviral vector pSEB61 was retrofitted in established HCT116-siKCN and SW480-siKCN cells to silence KCNQ1OT1. Cellular proliferation was measured using CCK8 assay, and flow cytometry (FCM) detected cell cycle changes. RNA sequencing (RNA-Seq) analysis showed differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to analyze enriched functions and signaling pathways. RT-qPCR, immunofluorescence, and western blotting were carried out to validate downstream gene expressions. The effects of tumorigenesis were evaluated in BALB/c nude mice by tumor xenografts. Our data revealed that the silencing of KCNQ1OT1 in HCT116 and SW480 cells slowed cell growth and decreased the number of cells in the G2/M phase. RNA-Seq analysis showed the data of DEGs enriched in various GO and KEGG pathways such as DNA replication and cell cycle. RT-qPCR, immunofluorescence, and western blotting confirmed downstream CCNE2 and PCNA gene expressions. HCT116-siKCN cells significantly suppressed tumorigenesis in BALB/c nude mice. Our study suggests that lncRNA KCNQ1OT1 may provide a promising therapeutic strategy for colon cancer.

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LIU, G., SHI, L., WANG, B., WU, Z., ZHAO, H. et al. (2024). Role of oncogenic long noncoding RNA KCNQ1OT1 in colon cancer. Oncology Research, 32(3), 585–596.



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