FAM46C inhibits cell proliferation and cell cycle progression and promotes apoptosis through PTEN/AKT signaling pathway and is associated with chemosensitivity in prostate cancer

Cholesteatoma is a benign keratinizing and hyper proliferative squamous epithelial lesion of the temporal bone. Epidermal growth factor (EGF) is one of the most important cytokines which has been shown to play a critical role in cholesteatoma. In this investigation, we studied the effects of EGF on the proliferation of keratinocytes and EGF-mediated signaling pathways underlying the pathogenesis of cholesteatoma. We examined the expressions of phosphorylated EGF receptor (p-EGFR), phosphorylated Akt (p-Akt), cyclinD1, and proliferating cell nuclear antigen (PCNA) in 40 cholesteatoma samples and 20 samples of normal external auditory canal (EAC) epithelium by immunohistochemical method. Furthermore,in vitrostudies were performed to investigate EGF-induced downstream signaling pathways in primary external auditory canal keratinocytes (EACKs). The expressions of p-EGFR, p-Akt, cyclinD1, and PCNA in cholesteatoma epithelium were significantly increased when compared with those of control subjects. We also demonstrated that EGF led to the activation of the EGFR/PI3K/Akt/cyclinD1 signaling pathway, which played a critical role in EGF-induced cell proliferation and cell cycle progression of EACKs. Both EGFR inhibitor AG1478 and PI3K inhibitor wortmannin inhibited the EGF-induced EGFR/PI3K/Akt/cyclinD1 signaling pathway concomitantly with inhibition of cell proliferation and cell cycle progression of EACKs. Taken together, our data suggest that the EGFR/PI3K/Akt/cyclinD1 signaling pathway is active in cholesteatoma and may play a crucial role in cholesteatoma epithelial hyper-proliferation. This study will facilitate the development of potential therapeutic targets for intratympanic drug therapy for cholesteatoma.

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Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway

Journal of Ovarian Research ◽

10.1186/s13048-021-00792-2 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Dongyong Yang ◽

Yanqing Wang ◽

Yajing Zheng ◽

Fangfang Dai ◽

Shiyi Liu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Structural Damage ◽

Polycystic Ovary ◽

Serum Insulin ◽

Tumor Cell Line ◽

Akt Signaling ◽

Akt Signaling Pathway

Abstract Background Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. Results CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. Conclusions Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.

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Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000485759 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1616-1628 ◽

Cited By ~ 7

Author(s):

Xin Jin ◽

Er Nie ◽

Xu Zhou ◽

Ailiang Zeng ◽

Tianfu Yu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Colony Formation ◽

Cell Cycle Progression ◽

Malignant Gliomas ◽

Treatment Strategies ◽

Cycle Progression ◽

Glioma Growth

Background: Gliomas result in the highest morbidity and mortality rates of intracranial primary central nervous system tumors because of their aggressive growth characteristics and high postoperative recurrence. They are characterized by genetic instability, intratumoral histopathological variability and unpredictable clinical behavior in patients. Proliferation is a key aspect of the clinical progression of malignant gliomas, complicating complete surgical resection and enabling tumor regrowth and further proliferation of the surviving tumor cells. Methods: The expression of Fstl1 was detected by western blotting and qRT-PCR. We used cell proliferation and colony formation assays to measure proliferation. Then, flow cytometry was used to analyze cell cycle progression. The expression of Fstl1, p-Smad1/5/8 and p21 in GBM tissue sections was evaluated using immunohistochemical staining. Furthermore, we used coimmunoprecipitation (Co-IP) and immunoprecipitation to validate the relationship between Fstl1, BMP4 and BMPR2. Finally, we used orthotopic xenograft studies to measure the growth of tumors in vivo. Results: We found that follistatin-like 1 (Fstl1) was upregulated in high-grade glioma specimens and that its levels correlated with poor prognosis. Fstl1 upregulation increased cell proliferation, colony formation and cell cycle progression, while its knockdown inhibited these processes. Moreover, Fstl1 interacted with bone morphogenetic protein (BMP) 4, but not BMP receptor (BMPR) 2, and competitively inhibited their association. Furthermore, Fstl1 overexpression suppressed the activation of the BMP4/Smad1/5/8 signaling pathway, while BMP4 overexpression reversed this effect. Conclusion: Our study demonstrated that Fstl1 promoted glioma growth through the BMP4/Smad1/5/8 signaling pathway, and these findings suggest potential new glioblastoma treatment strategies.

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TRIM44 is indispensable for glioma cell proliferation and cell cycle progression through AKT/p21/p27 signaling pathway

Journal of Neuro-Oncology ◽

10.1007/s11060-019-03301-0 ◽

2019 ◽

Vol 145 (2) ◽

pp. 211-222 ◽

Cited By ~ 6

Author(s):

Xia Zhou ◽

Yadong Yang ◽

Pengcheng Ma ◽

Na Wang ◽

Dong Yang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathway ◽

Glioma Cell ◽

Cell Cycle Progression ◽

Cycle Progression ◽

Glioma Cell Proliferation

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

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504019x15732109856009 ◽

2020 ◽

Vol 28 (2) ◽

pp. 147-159 ◽

Cited By ~ 4

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.

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ANKHD1, a novel component of the Hippo signaling pathway, promotes YAP1 activation and cell cycle progression in prostate cancer cells

Experimental Cell Research ◽

10.1016/j.yexcr.2014.04.004 ◽

2014 ◽

Vol 324 (2) ◽

pp. 137-145 ◽

Cited By ~ 34

Author(s):

João Agostinho Machado-Neto ◽

Mariana Lazarini ◽

Patricia Favaro ◽

Gilberto Carlos Franchi ◽

Alexandre Eduardo Nowill ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Signaling Pathway ◽

Cell Cycle Progression ◽

Hippo Signaling ◽

Prostate Cancer Cells ◽

Cycle Progression ◽

Hippo Signaling Pathway

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CNTN-1 promotes docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

Archives of Medical Science ◽

10.5114/aoms.2020.92939 ◽

2021 ◽

Vol 17 (1) ◽

pp. 152-165 ◽

Cited By ~ 1

Author(s):

Binshen Chen ◽

Yiming Zhang ◽

Chaoming Li ◽

Peng Xu ◽

Yubo Gao ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Drug Resistance ◽

Signaling Pathway ◽

Akt Signaling ◽

Cell Counting ◽

Multi Drug Resistance ◽

Akt Signaling Pathway ◽

Mesenchymal Transition

IntroductionTherapy options for prostate cancer (PCa) typically are centered on docetaxel-based chemotherapy but are limited by the effects of multi-drug resistance. Recent advances have illustrated a role of contactin-1 (CNTN-1) in tumor chemoresistance, while the function and mechanism of CNTN-1 in the resistance of docetaxel in prostate cancer have not yet been elucidated.Material and methodsDocetaxel (Dox)-resistant PCa cell lines of PC3 (PC3-DR) and DU145 (DU145-DR) were established, and short hairpin RNA (shRNA) constructs targeting CNTN-1 were generated to analyze the effect of knockdown of CNTN-1 on PCa progression. Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing, transwell and western blotting analysis were used to analyze cell proliferation, apoptosis, migration, invasion and related protein expression levels, respectively.ResultsKnockdown of CNTN-1 in PC3-DR and DU145-DR cells attenuated cell proliferation, migration, invasion, EMT phenotype, and drug resistance, and increased cell apoptosis further reduced the tumorigenic phenotype. Knockdown of CNTN-1 resulted in an anti-tumor effect in the xenograft tumor model, and decreased activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway both in vitro and in vivo.ConclusionsThe results of the present study suggest that downregulation of CNTN-1 may be an important mechanism to reverse chemoresistance in Dox-resistant PCa progression, thus shedding light on the development of novel anti-tumor therapeutics for the treatment of PCa.

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

Cancer Cell International ◽

10.1186/s12935-019-1026-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

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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