LncRNA GHET1 promotes cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways

Abstract

Cervical cancer (CC) is a prevalent gynecological cancer, and the patients with CC usually suffer from dismal prognosis. Long non-coding RNAs (lncRNAs) are demonstrated to serve as promising biological targets in human cancers. Gastric carcinoma proliferation enhancing transcript 1 (GHET1) has been revealed to function as an oncogene in several cancers, but it has never been investigated in CC. We proposed to examine the biological role of GHET1 in CC and the underlying mechanism and validated the up-regulated expression of GHET1 in CC cell lines. Loss-of-function assays demonstrated that down-regulation of GHET1 inhibited cell growth, migration and epithelial-to-mesenchymal transition (EMT) in CC. Furthermore, we validated that GHET1 down-regulation could inactivate AKT/mTOR and Wnt/β-catenin pathways, and that respective activation of these two pathways abrogated the inhibitive effect of GHET1 knockdown on CC cell growth, migration and EMT. Moreover, we unfolded a preliminary investigation on the modulation of GHET1 on AKT/mTOR and Wnt/β-catenin pathways. We found that GHET1 stabilized E2F6 mRNA through interacting with IGF2BP2, so as to regulate the activity of AKT/mTOR and Wnt/β-catenin pathways. Rescue assays also proved that GHET1 regulated these two pathways and CC cell growth, migration and EMT through E2F6. In conclusion, we revealed that down-regulation of GHET1 suppresses cervical cancer progression through regulating AKT/mTOR and Wnt/β-catenin signaling pathways, indicating GHET1 as a promising molecular biomarker for CC treatment improvement.

<p>Knockdown of MIR4435-2HG Suppresses the Proliferation, Migration and Invasion of Cervical Cancer Cells via Regulating the miR-128-3p/MSI2 Axis in vitro</p>

“…CC cells. 28 In the current study, we found that lncRNA MIR4435-2HG knockdown suppressed the viability, migration ability and invasion ability of CC cells. Similar to our results, a recent study has demonstrated that the proliferation, invasion and migration of CRC cells can be inhibited by MIR4435-2HG knockdown.…”

Six-lncRNA Immune Prognostic Signature for Cervical Cancer

“…Previous studies have shown that activation of the Wnt signaling pathway is the first step in carcinogenesis of the cervix ( Uren et al, 2005 ). The Wnt signaling pathway regulates proliferation, migration, and chemoradiation tolerance in cervical cancer cells and is associated with poor clinical outcomes ( Bahrami et al, 2017 ; Yang et al, 2018 ; Liu et al, 2020d ). Drews et al (2019) found that E6 degrades NHERF1 to regulate the Wnt signaling pathway and affect the progression of cervical cancer.…”

Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

“…Most of the previous research on IGF2BP2 has focused on its role as a retinol-binding protein (RBP) targeting downstream transcription factors to regulate post-transcriptional translational carcinogenesis. In cervical cancer, gastric carcinoma proliferation enhancing transcript 1 (GHET1) regulates AKT/mTOR and Wnt/β-catenin signaling pathways by stabilizing the interaction of E2F6 and IGF2BP2 (Liu et al, 2020). Non-coding genes can also target IGF2BP2 directly: the lncRNA HOTAIR inhibits IGF2BP2 and regulates colon cancer growth and invasion (Wu et al, 2018).…”