Abstract
Long non-coding RNAs (lncRNAs) have shown to act as important regulators in cancer biology. The aim of this study was to investigate the role and mechanism of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) in colorectal cancer (CRC) progression. The abundance of KCNQ1OT1, microRNA-216b-5p (miR-216b-5p) and zinc finger protein 146 (ZNF146) messenger RNA (mRNA) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Cell migration and invasion abilities were assessed by transwell assays. Western blot assay was performed for determination of protein levels. LncBase v.2 of DIANA Tool and StarBase software were used to predict the targets of KCNQ1OT1 and miR-216b-5p, respectively. Dual-luciferase reporter assay was implemented to confirm the target interaction between miR-216b-5p and KCNQ1OT1 or ZNF146. KCNQ1OT1 expression was higher in CRC tissues and cell lines. KCNQ1OT1 interference restrained the proliferation, migration and invasion of CRC cells. MiR-216b-5p was a target of KCNQ1OT1 in CRC cells, and KCNQ1OT1 knockdown-induced effects in CRC cells were partly overturned by miR-216b-5p silencing. MiR-216b-5p bound to the 3′ untranslated region (3′UTR) of ZNF146, and ZNF146 overexpression partly attenuated miR-216b-5p overexpression-mediated influences in CRC cells. KCNQ1OT1 up-regulated the abundance of ZNF146 through sequestering miR-216b-5p in CRC cells. KCNQ1OT1 accelerated the proliferation and motility of CRC cells through elevating ZNF146 expression via sponging miR-216b-5p. KCNQ1OT1/miR-216b-5p/ZNF146 axis might be underlying target for the diagnosis and treatment of CRC patients.
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The data that support the findings of this study are available on request from the corresponding author.
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The authors wish to thank the pathology department of Henan Cancer Hospital for providing clinical samples.
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SZ and YH designed the study, performed the majority of experiments and drafted the manuscript; C-YC checked and corrected the grammer errors in the manuscript.
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The CRC patients were enrolled in this study with written informed consents.
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Zhu, S., Chen, CY. & Hao, Y. LncRNA KCNQ1OT1 acts as miR-216b-5p sponge to promote colorectal cancer progression via up-regulating ZNF146. J Mol Histol 52, 479–490 (2021). https://doi.org/10.1007/s10735-020-09942-0
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DOI: https://doi.org/10.1007/s10735-020-09942-0