scholarly journals PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma

Oncogene ◽  
2021 ◽  
Author(s):  
Wen-Ting Yang ◽  
Mei Chen ◽  
Rui Xu ◽  
Peng-Sheng Zheng
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Zinc Finger Protein ◽  
Akt Signaling ◽  
Cervical Cancer Cell ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Tumorigenic Potential

AbstractPR domain zinc finger protein 4 (PRDM4) is a transcription factor that plays key roles in stem cell self-renewal and tumorigenesis. However, its biological role and exact mechanism in cervical cancer remain unknown. Here, both immunohistochemistry (IHC) and Western blot assays demonstrated that the expression of PRDM4 in cervical cancer tissues was much lower than that in the normal cervix. A xenograft assay showed that PRDM4 overexpression in the cervical cancer cell lines SiHa and HeLa dramatically inhibited cell proliferation and tumorigenic potential in vivo. Conversely, the silencing of PRDM4 promoted cervical cancer cell proliferation and tumorigenic potential. Mechanistically, PRDM4 induced cell cycle arrest at the transition from G0/G1 phase to S phase by upregulating p27 and p21 expression and downregulating Cyclin D1 and CDK4 expression. Furthermore, the PI3K/AKT signaling pathway was inactivated in PRDM4-overexpressing cells, which decreased the levels of p-AKT and upregulated the expression of PTEN, an inhibitor of the PI3K/AKT signaling pathway, at both the transcriptional and translational levels. Dual-luciferase reporter assays and qChIP assays confirmed that PRDM4 transactivated the expression of PTEN by binding to two specific regions in the PTEN promoter. Furthermore, PTEN silencing or a PTEN inhibitor rescued the cell defects induced by PRDM4 overexpression. Therefore, our data suggest that PRDM4 inhibits cell proliferation and tumorigenesis by downregulating the activity of the PI3K/AKT signaling pathway by directly transactivating PTEN expression in cervical cancer.

scholarly journals MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC

2020 ◽  
Vol 28 (2) ◽  
pp. 147-159 ◽  
Author(s):  
ZiJun Liao ◽  
Qi Zheng ◽  
Ting Wei ◽  
YanBing Zhang ◽  
JieQun Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Exogenous Expression ◽  
Induced Apoptosis

MicroRNAs (miRNAs) play crucial roles in tumorigenesis and tumor progression. miR-561 has been reported to be downregulated in gastric cancer and affects cancer cell proliferation and metastasis. However, the role and underlying molecular mechanism of miR-561 in human non-small cell lung cancer (NSCLC) remain unknown and need to be further elucidated. In this study, we discovered that miR-561 expression was downregulated in human NSCLC tissues and cell lines. The overexpression of miR-561 inhibited NSCLC cell proliferation and cell cycle G1/S transition and induced apoptosis. The inhibition of miR-561 facilitated cell proliferation and G1/S transition and suppressed apoptosis. miR-561 expression was inversely correlated with P-REX2a expression in NSCLC tissues. P-REX2a was confirmed to be a direct target of miR-561 using a luciferase reporter assay. The overexpression of miR-561 decreased P-REX2a expression, and the suppression of miR-561 increased P-REX2a expression. Particularly, P-REX2a silencing recapitulated the cellular and molecular effects observed upon miR-561 overexpression, and P-REX2a overexpression counteracted the effects of miR-561 overexpression on NSCLC cells. Moreover, both exogenous expression of miR-561 and silencing of P-REX2a resulted in suppression of the PTEN/AKT signaling pathway. Our study demonstrates that miR-561 inhibits NSCLC cell proliferation and G1/S transition and induces apoptosis through suppression of the PTEN/AKT signaling pathway by targeting P-REX2a. These findings indicate that miR-561 plays a significant role in NSCLC progression and serves as a potential therapeutic target for NSCLC.

scholarly journals TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

2021 ◽  
Vol 10 ◽  
Author(s):  
Mengya Zhong ◽  
Xingfeng Qiu ◽  
Yu Liu ◽  
Yan Yang ◽  
Lei Gu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Hct116 Cells ◽  
Proliferation And Migration

Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

scholarly journals ICAT Promotes Cervical Cancer Cell Proliferation, Invasion, Migration and Epithelial‑to‑mesenchymal Transition Through HPV16 E6, E7/ miR-23b-3p/ ICAT Axis

2021 ◽  
Author(s):  
Jing Hu ◽  
Zijiu Sun ◽  
Hui Wang ◽  
Wei Ren ◽  
Yuting Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Recombinant Adenovirus ◽  
Cervical Cancer Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Hpv 16 ◽  
Hpv16 E6 ◽  
Mesenchymal Transition

Abstract Background: Human papillomavirus (HPV) 16 plays a crucial role in cervical cancer (CC) development. Previous study reported that inhibitor of β-catenin and TCF (ICAT) is upregulated in CC and promotes cervical tumor progression. Herein, we aimed to investigate the underlying molecular mechanism that HPV16 regulates the expression of ICAT and promotes the CC development. Methods: The expressions of HPV 16 E6, E7 and ICAT were modulated by small interfering RNA and recombinant adenovirus, respectively. qRT-PCR was conducted to detect the mRNA expression of HPV 16 E6, E7, ICAT and miR-23b-3p in SiHa and CasKi cells. Bioinformatics analysis was utilized to predict the potential miRNAs that could bind to the ICAT 3′ untranslated region. Then, the dual luciferase reporter assay was used to confirm that. Cell proliferation ability was detected by CCK-8 assay. Wound healing and Transwell assays were used to observe migration and invasion abilities. Protein expressions were measured with western blot. Results: Results revealed that after knocking down of HPV16 E6, E7, the expression of ICAT decreased, but the expression of miR-23b-3p increased. Besides, miR-23b-3p negatively modulated ICAT expression in HPV16 positive CC cells. Dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of SiHa and CasKi cells, such as migration, invasion and EMT. Importantly, the overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16 positive cervical cancer cell. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CasKi cells.Conclusions: Our study demonstrates that HPV 16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16 positive CC pathogenesis, which may serve as a promising therapy target for HPV 16-associated cervical cancer.

scholarly journals MicroRNA-1269 promotes cell proliferation via the AKT signaling pathway by targeting RASSF9 in human gastric cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wen-Li Liu ◽  
Hu-xia Wang ◽  
Cheng-xin Shi ◽  
Fei-yu Shi ◽  
Ling-yu Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Target Gene ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Akt Signaling Pathway ◽  
Qrt Pcr

Abstract Background MicroRNAs (miRNAs) play key roles in tumorigenesis and progression of gastric cancer (GC). miR-1269 has been reported to be upregulated in several cancers and plays a crucial role in carcinogenesis and cancer progression. However, the biological function of miR-1269 in human GC and its mechanism remain unclear and need to be further elucidated. Methods The expression of miR-1269 in GC tissues and cell lines was detected by quantitative real-time PCR (qRT-PCR). Target prediction programs (TargetScanHuman 7.2 and miRBase) and a dual-luciferase reporter assay were used to confirm that Ras-association domain family 9 (RASSF9) is a target gene of miR-1269. The expression of RASSF9 was measured by qRT-PCR and Western blotting in GC tissues. MTT and cell counting assays were used to explore the effect of miR-1269 on GC cell proliferation. The cell cycle and apoptosis were measured by flow cytometry. RASSF9 knockdown and overexpression were used to further verify the function of the target gene. Results We found that miR-1269 expression was upregulated in human GC tissues and cell lines. The overexpression of miR-1269 promoted GC cell proliferation and cell cycle G1-S transition and suppressed apoptosis. The inhibition of miR-1269 inhibited cell growth and G1-S transition and induced apoptosis. miR-1269 expression was inversely correlated with RASSF9 expression in GC tissues. RASSF9 was verified to be a direct target of miR-1269 by using a luciferase reporter assay. The overexpression of miR-1269 decreased RASSF9 expression at both the mRNA and protein levels, and the inhibition of miR-1269 increased RASSF9 expression. Importantly, silencing RASSF9 resulted in the same biological effects in GC cells as those induced by overexpression of miR-1269. Overexpression of RASSF9 reversed the effects of miR-1269 overexpression on GC cells. Both miR-1269 overexpression and RASSF9 silencing activated the AKT signaling pathway, which modulated cell cycle regulators (Cyclin D1 and CDK2). In contrast, inhibition of miR-1269 and RASSF9 overexpression inhibited the AKT signaling pathway. Moreover, miR-1269 and RASSF9 also regulated the Bax/Bcl-2 signaling pathway. Conclusions Our results demonstrate that miR-1269 promotes GC cell proliferation and cell cycle G1-S transition by activating the AKT signaling pathway and inhibiting cell apoptosis via regulation of the Bax/Bcl-2 signaling pathway by targeting RASSF9. Our findings indicate an oncogenic role of miR-1269 in GC pathogenesis and the potential use of miR-1269 in GC therapy.

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