MiR-552-3p promotes malignant progression of gallbladder carcinoma by reactivating the Akt/β-catenin signaling pathway due to inhibition of the tumor suppressor gene RGMA

Abstract Background Dysregulation of microRNA (miRNA) expression in various cancers and their vital roles in malignant progression of cancers are well investigated. Our previous studies have analyzed miRNAs that promote malignant progression of hepatocellular carcinoma (HCC), this study aim to systematically elucidate metastasis suppressor miRNAs in HCC. Methods High-throughput RNA sequencing analysis was used to identify anti-metastatic miRNAs of HCC. The relative expression levels of miRNAs were confirmed by qRT-PCR. The biological functions of miRNAs were studied by CCK8, wound-healing, transwell, colony formation in HCC cells. Circulating tumor cells were enriched from blood samples of HCC patients and cultured by three-dimensional (3D) system. The potential target mRNAs of miRNAs were analyzed by bioinformatics analysis and confirmed by luciferase reporter assay. Liver metastasis model via tail vein injection was further examined in nude mice. Kaplan-Meier and Cox regression were used to analyze the value of potential target mRNAs on overall survival. Results miR-2392 was significantly down-regulated in HCC. Overexpression of miR-2392 suppressed proliferation, mobility, spheroid formation and maintenance of cancer stem cells (CSC)-like characteristics in HCC cell lines, whereas down-regulation of miR-2392 led to the opposite results. CTCs from HCC patients with lower serum miR-2392 level had stronger cell spheroid formation ability. A negative correlation between the content of miR-2392 in serum and the number of CTC spheroids had been found. We identified Jagged2 (JAG2) as a direct target of miR-2392, miR-2392 inhibited the expression and nuclear accumulation of JAG2 by targeting 3’-UTR of JAG2. HCC cells were treated with LV-miR-2392 inhibitor and JAG2-siRNA to explore the mechanism of miR-2392 and JAG2 on HCC. Down-regulation of JAG2 inhibited the overexpression effects of miR-2392 in vitro and in vivo. JAG2 is highly expressed in HCC and is closely related to poor prognosis and survival of patients. Conclusions Our findings indicated a significant role of the miR-2392/JAG2 axis in suppressing HCC cell growth and aggressiveness, miR-2392 may play a role as a tumor suppressor gene to guide the individualized precise treatment of HCC.

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Regulation of carcinogenesis and modulation through Wnt/β-catenin signaling by curcumin in an ovarian cancer cell line

Scientific Reports ◽

10.1038/s41598-019-53509-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 8

Author(s):

Hsing-Yu Yen ◽

Chih-Wei Tsao ◽

Ya-Wen Lin ◽

Chih-Chi Kuo ◽

Chang-Huei Tsao ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Suppressor ◽

Cell Line ◽

Tumor Suppressor Gene ◽

Signaling Pathway ◽

Cancer Cell ◽

Ovarian Cancer Cell ◽

Ovarian Cancer Cell Line ◽

Cancer Cell Line ◽

Suppressor Gene

AbstractThe secreted frizzled-related protein 5 gene (SFRP5) that antagonize the Wnt/β-catenin signaling is frequently inactivated by promoter methylation and oncogenic activation of the Wnt signaling pathway is common in many cancers. The curcumin-rich Curcuma longa has been reported to potent anti-cancer property involved in epigenetic regulation to inhibit tumor suppressor gene methylation and re-expression. In a compounds screening, we found that curcumin can inhibit Wnt/β-catenin signaling. Therefore, the aim of this study was to investigate the effects of curcumin on SFRP5 DNA methylation modification in an ovarian cancer cell line (SKOV3). SKOV3 cells were treated with DMSO, 10 μM 5-aza-2′-deoxycytidine (DAC), 5 μM DAC, 20 μM curcumin, and 20 μM curcumin combined with 5 μM DAC for 96 hours, following which RNA and proteins were extracted for further analysis. The results showed that curcumin combined with 5 μM DAC may inhibit cancer cell colony formation, migration through EMT (epithelial–mesenchymal transition) process regulation, total DNMT activity, especially in DNMT3a protein expression, and may also regulate tumor suppressor gene SFRP5 expression involved in the Wnt/β-catenin signaling pathway. The combined treatment attenuated ovarian cancer development.

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Microrna-2392 Functions as a Tumor Suppressor Gene and Inhibits Malignant Progression of Hepatocellular Carcinoma Via Directly Targeting JAG2

10.21203/rs.3.rs-484869/v1 ◽

2021 ◽

Author(s):

Bin Sun ◽

Weidan Ji ◽

Chunying Liu ◽

Xuejing Lin ◽

Lei Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene ◽

Malignant Progression ◽

Nuclear Accumulation ◽

Metastasis Suppressor ◽

Spheroid Formation ◽

Down Regulation

Abstract Background Dysregulation of microRNA (miRNA) expression in various cancers and their vital roles in malignant progression of cancers are well investigated. Our previous studies have analyzed miRNAs that promote malignant progression of hepatocellular carcinoma (HCC), this study aim to systematically elucidate metastasis suppressor miRNAs in HCC. Results miR-2392 was significantly down-regulated in HCC. Overexpression of miR-2392 suppressed proliferation, mobility, spheroid formation and maintenance of cancer stem cells (CSC)-like characteristics in HCC cell lines, whereas down-regulation of miR-2392 led to the opposite results. CTCs from HCC patients with lower serum miR-2392 level had stronger cell spheroid formation ability. A negative correlation between the content of miR-2392 in serum and the number of CTC spheroids had been found. We identified Jagged2 (JAG2) as a direct target of miR-2392, miR-2392 inhibited the expression and nuclear accumulation of JAG2 by targeting 3’-UTR of JAG2. HCC cells were treated with LV-miR-2392 inhibitor and JAG2-siRNA to explore the mechanism of miR-2392 and JAG2 on HCC. Down-regulation of JAG2 inhibited the overexpression effects of miR-2392 in vitro and in vivo. JAG2 is highly expressed in HCC and is closely related to poor prognosis and survival of patients. Conclusions Our findings indicated a significant role of the miR-2392/JAG2 axis in suppressing HCC cell growth and aggressiveness, miR-2392 may play a role as a tumor suppressor gene to guide the individualized precise treatment of HCC.

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