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

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.

LncRNAs could play a vital role in osteosarcoma treatment: Inhibiting osteosarcoma progression and improving chemotherapy resistance

“…CCK-8 assays showed that RNAH19 knockdown increased miR-29a-3p expression and decreased LASP1 expression, which inhibited Saos2 and MG63 cell proliferation. Huang et al (2021) confirmed significantly inhibited proliferation and colony formation in U2OS and SAOS-2 cells after lncRNA KCNQ1OT1knockdown, as assessed by CCK-8 assay, colony formation assay, and western blot analysis. The authors suggested that lncRNA KCNQ1OT1 promoted tumor growth and activated the Wnt/ β catenin signaling pathway in OS by targeting the miR3666/ KLF7 axis.…”

A novel risk score model based on glycolysis‐related genes and a prognostic model for predicting overall survival of osteosarcoma patients

“…Li et al 28 reported TGFβ signaling pathway was involved in the progression and metastasis of osteosarcoma. Huang et al 29 revealed LncRNA KCNQ1OT1 promoted osteosarcoma growth by activating Wnt/β catenin signaling. Li et al 30 showed base excision repair and DNA replication in osteosarcoma can be blocked by inhibition of ATR‐Chk1 signaling.…”

Screening for MicroRNA combination with engineered exosomes as a new tool against osteosarcoma in elderly patients

“…The Kruppel-like factor 11 (KLF11) is expressed in a wide variety of tissues and controls proliferation, differentiation, and apoptosis ( Wang et al, 2021b ). MiR-3666/KLF7 axis, as the downstream target of KCNQ1OT1, regulate tumor growth ( Huang et al, 2021 ). The zinc finger protein YY1 belongs to the GLI-Kruppel class and is widely distributed throughout the human body ( Kwiatkowska et al, 2022 ).…”