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.
Highlights
As a familiar gynecological cancer, cervical cancer (CC) accounts for a large proportion of tumor-resulted deaths globally [1,2]
E-cadherin expression was enhanced, whereas N-cadherin expression was decreased upon gastric carcinoma proliferation enhancing transcript 1 (GHET1) knockdown in CC cells (Figure 1E), indicating that GHET1 suppression might inhibit epithelial-to-mesenchymal transition (EMT) progression in CC cells. These results suggested that GHET1 was up-regulated in CC cells and its down-regulation inhibited proliferation, migration and EMT
long non-coding RNA (LncRNA) are increasingly illustrated by mounting studies to have significant impact on cancer regulation [6,7], including in cervical cancer [8]
Summary
As a familiar gynecological cancer, cervical cancer (CC) accounts for a large proportion of tumor-resulted deaths globally [1,2]. There are various therapeutic regimes accessible to CC patients, including tumor dissection and chemo- or radiotherapies, only approximately 40% of CC patients could survive for more than 5-years [3,4]. Mounting studies have demonstrated that dysregulated lncRNAs have close relation to tumorigenesis and progression of human cancers [6,7], including CC [8]. Gastric carcinoma proliferation enhancing transcript 1 (GHET1) is a lncRNA suggested by several studies as an oncogene in cancers, such as breast cancer [9], colorectal cancer [10] and gastric cancer [11]. The role of GHET1 has not been explored in cervical cancer
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