Long noncoding RNA KCNQ1OT1 contributes to tumor growth and activates Wnt/β‑catenin signaling in osteosarcoma by targeting the miR‑3666/KLF7 axis

Huang,Aijun; Jin,Song; Han,Weidong; Wang,Yiming; Ma,Shuqiang; Wang,Zengrong; Lin,Kun; Zou,Qingbao; Zhou,Jingying; Li,Zhongtan; Chen,Liping

doi:10.3892/ijmm.2020.4768

Long noncoding RNA KCNQ1OT1 contributes to tumor growth and activates Wnt/β‑catenin signaling in osteosarcoma by targeting the miR‑3666/KLF7 axis

Authors:
- Aijun Huang
- Song Jin
- Weidong Han
- Yiming Wang
- Shuqiang Ma
- Zengrong Wang
- Kun Lin
- Qingbao Zou
- Jingying Zhou
- Zhongtan Li
- Liping Chen
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Affiliations: Department of Orthopaedic Surgery, The Eighth Affiliated Hospital, Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China, Department of Orthopaedic Surgery, The Eighth Affiliated Hospital, Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China, Department of Pain Medicine, The Eighth Affiliated Hospital, Sun Yat‑Sen University, Shenzhen, Guangdong 518033, P.R. China, Department of Nephrology, The Second People's Hospital of Futian District, Shenzhen, Guangdong 518049, P.R. China
Published online on: October 23, 2020 https://doi.org/10.3892/ijmm.2020.4768
Pages: 387-396

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Abstract

Osteosarcoma (OS) is a type of primary malignant cancer occurring in the bone and poses a threat to the lives of children and young adults. Long non‑coding RNAs (lncRNAs) have been certified to play important roles in various human malignant tumors, including OS. lncRNA KCNQ1OT1 has been investigated in certain types of cancer; however, its role and molecular mechanisms in OS remain to be determined. In the present study, a high KCNQ1OT1 expression was detected in human OS tissues and cell lines. Moreover, patients with OS with a high expression of KCNQ1OT1 presented a worse prognosis. Loss‑of‑function assays demonstrated that KCNQ1OT1 silencing suppressed cell proliferative, migratory and invasive abilities in OS. Importantly, the knockdown of KCNQ1OT1 suppressed the Wnt/β‑catenin signaling pathway in OS. In vivo assays displayed the inhibitory role of the silencing of KCNQ1OT1 in OS tumor growth. As regards the underlying mechanisms, KCNQ1OT1 could sponge miR‑3666, and its expression was negatively associated with that of miR‑3666 in OS tissues. Thereafter, Kruppel‑like factor 7 (KLF7), upregulated in OS tissues and cells, was discerned as a target gene of miR‑3666. Furthermore, KLF7 expression negatively correlated with miR‑3666 expression, whereas it positively correlated with KCNQ1OT1 expression. A rescue assay delineated that the overexpression of KLF7 counteracted the KCNQ1OT1 knockdown‑induced suppression of OS cell proliferation, migration, invasion and Wnt/β‑catenin signaling. Collectively, the present study demonstrates that KCNQ1OT1 facilitates OS progression and activates Wnt/β‑catenin signaling by targeting the miR‑3666/KLF7 axis.

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