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.
Cervical cancer (CC) is known as one of the most common gynecological tumors. Long noncoding RNAs (lncRNAs) are a group of regulators that have been widely reported in human malignant tumors including CC. On the basis of the data of The Cancer Genome Atlas, lncRNA DDN and PRKAG1 antisense RNA 1 (DDN-AS1) that is overexpressed in CC tissues predicted poor prognosis for patients with CC. Moreover, quantitative reverse transcription PCR analysis further identified the upregulation of DDN-AS1 in CC tissues and cell lines.Loss-of-function assays revealed that knockdown of DDN-AS1 suppressed CC progression by efficiently inhibiting cell proliferation, migration, and invasion.Mechanism investigations revealed that DDN-AS1 was upregulated by its upstream transcription activator transcription factor 3 (TCF3). Moreover, DDN-AS1 increased the expression of TCF3 by competitively binding miR-15aand miR-16. In conclusion, DDN-AS1-miR-15a/16-TCF3 feedback loop contributes to cell proliferation, migration, and invasion in CC. K E Y W O R D Scervical cancer, lncRNA DDN and PRKAG1 antisense RNA 1, migration, miR-15a/16, transcription factor 3
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