<p>CREB1 Suppresses Transcription of microRNA-186 to Promote Growth, Invasion and Epithelial–Mesenchymal Transition of Gastric Cancer Cells Through the KRT8/HIF-1α Axis</p>

Abstract

Background: The cAMP response element-binding protein 1 (CREB1) was initiated as a potential target for cancer treatment. This research was conducted to probe the effect of CREB1 in the progression of gastric cancer (GC) and the molecules involved. Materials and Methods: CREB1 expression in GC tissues and cell lines (AGS and MKN-45) as well as that in normal tissues and in gastric mucosa cell line (GES-1) was detected. The correlation between CREB1 expression and prognosis of GC patients was determined. Artificial silencing of CREB1 was introduced to evaluate its effect on biological behaviors of GC cells. The target microRNA (miRNA) of CREB1 and the target mRNA of miR-186 were predicted and validated. Altered expression of miR-186, KRT8 and HIF-1α was introduced to confirm their functions in GC progression. Results: CREB1 was abundantly expressed in GC tissues and cells and linked to dismal prognosis in patients. Silencing of CREB1 or upregulation of miR-186 suppressed the malignant behaviors such as growth, epithelial-mesenchymal transition (EMT) and invasion of GC cells, while artificial overexpression of KRT8 led to reversed trends. KRT8 was a target mRNA of miR-186, and CREB1 transcriptionally suppressed miR-186 expression to further up-regulate KRT8. KRT8 was also found to increase HIF-1α expression. Upregulation of HIF-1α was found to block the suppressing role of CREB1 silencing in GC cell malignancy. Conclusion: This study evidenced that silencing of CREB1 inhibits growth, invasion, EMT and resistance to apoptosis of GC cells involving the upregulation of miR-186 and the following downregulation of KRT8 and HIF-1α.

miR‐450a exerts oncosuppressive effects in breast carcinoma by targeting CREB1

“…CREB1 is abundantly upregulated in gastric cancer and high expression of CREB1 is associated with dismal prognosis in patients. 25 CREB1 is upregulated in bladder cancer and knockdown of CREB1 inhibits cell proliferative and invasive capacities. 26 These results substantiate our finding that CREB1 acts as a cancerpromoting gene in cancer.…”

“…In this study, we also discovered that attenuation of CREB1 expression exerted a similar effect as miR‐450a in breast cancer cell growth and invasion. CREB1 is abundantly upregulated in gastric cancer and high expression of CREB1 is associated with dismal prognosis in patients 25 . CREB1 is upregulated in bladder cancer and knockdown of CREB1 inhibits cell proliferative and invasive capacities 26 .…”

MiR-654-3p Constrains Proliferation, Invasion, and Migration of Sinonasal Squamous Cell Carcinoma via CREB1/PSEN1 Regulatory Axis

“…But when compared with miR-mimc + oe-NC group, the apoptotic ratio of cells in miR-mimic + oe-CREB1 group was noticeably downregulated, demonstrating that the promoting effect of miR-654-3p on SNSCC cell apoptosis was reversed by CREB1. Moreover, numerous studies reported that CREB1 overexpression is associated with epithelial–mesenchymal transition (EMT) of cancer cells in a variety of cancers ( Yan et al, 2018 ; Dong et al, 2019 ; Ma et al, 2019 ; Huang et al, 2020 ). On account of previous studies, we supposed that CREB1 may affect the EMT process of SNSCC cells; therefore, we carried out Western blotting to measure the expression levels of EMT-related proteins in each transfection group ( Figure 3F ).…”

The Roles of the Colon Cancer Associated Transcript 2 (CCAT2) Long Non-Coding RNA in Cancer: A Comprehensive Characterization of the Tumorigenic and Molecular Functions

“…Additionally, CCAT2 was found to modulate the EMT phenotype through cAMP-responsive element-binding protein 1 (CREB1) expression modulation [96]. CREB1 is an oncogene that was shown to promote tumor cell proliferation, EMT transition, and metastasis in gastric cancer, CRC, and prostate cancer [102,103]. CREB1 was shown to be a target of the tumor suppressor miR-493-5p.…”