The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro

Serine/threonine protein kinase-3 (STK3) is a critical molecule of the Hippo pathway but little is known about its biological functions in the ovarian cancer development. We demonstrated the roles of STK3 in ovarian cancer. Existing databases were used to study the expression profile of STK3. STK3 was significantly downregulated in OC patients, and the low STK3 expression was correlated with a poor prognosis. In vitro cell proliferation, apoptosis, and migration assays, and in vivo subcutaneous xenograft tumor models were used to determine the roles of STK3. The overexpression of STK3 significantly inhibited cell proliferation, apoptosis, and migration of ovarian cancer cells in vitro and tumor growth in vivo. Bisulfite sequencing PCR analysis was performed to validate the methylation of STK3 in ovarian cancer. RNA sequencing and gene set enrichment analysis (GSEA) were used to compare the transcriptome changes in the STK3 overexpression ovarian cancer and control cells. The signaling pathway was analyzed by western blotting. STK3 promoted the migration of CD8+ T-cells by activating nuclear transcription factor κB (NF-κB) signaling. STK3 is a potential predictor of OC. It plays an important role in suppressing tumor growth of ovarian cancer and in chemotaxis of CD8+ T-cells.

Download Full-text

Cordyceps militaris Exerts Antitumor Effect on Carboplatin-Resistant Ovarian Cancer via Activation of ATF3/TP53 Signaling In Vitro and In Vivo

Natural Product Communications ◽

10.1177/1934578x20902558 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1934578X2090255

Author(s):

Eunbi Jo ◽

Hyun-Jin Jang ◽

Kyeong E. Yang ◽

Min S. Jang ◽

Yang H. Huh ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

B Cell Lymphoma ◽

Cordyceps Militaris ◽

Exponential Growth Phase ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Parp 1

This study aimed to investigate the effect of Cordyceps militaris extract on the proliferation and apoptosis of carboplatin- resistant SKOV-3 and determine the underlying mechanisms for overcoming carboplatin resistance in human ovarian cancer. We cultured the carboplatin-resistant SKOV-3 cells in vitro until the exponential growth phase and then treated with different concentrations of C. militaris for 24, 48, and 72 hours. We performed cell proliferation assay, cell morphological change assessment using transmission electron microscopy, apoptosis assay, and immunoblotting to measure the protein expression of caspase-3 and -8, poly (ADP-ribose) polymerase (PARP)-1, B-cell lymphoma (Bcl)-2, and activating transcription factor 3 (ATF3)/TP53 signaling-related proteins. As a result, C. militaris reduced the viability of carboplatin-resistant SKOV-3 and induced morphological disruptions in a dose- and time-dependent manner. The gene expression profiles indicated a reprogramming pattern of the previously known and unknown genes and transcription factors associated with the action of TCTN3 on carboplatin-resistant SKOV-3 cells. We also confirmed the C. militaris-induced activation of the ATF3/TP53 pathway. Immunoblotting indicated that cotreatment of C. militaris and carboplatin-mediated ATF3/TP53 upregulation induced apoptosis in the carboplatin-resistant SKOV-3 cells, which are involved in the serial activation of pro-apoptotic proteins, including Bcl-2, Bax, caspases, and PARP-1. Further, when the ATF3 and TP53 expression increased, the CHOP and PUMA expressions were upregulated. Consequently, the upregulated CHOP/PUMA expression activated the positive regulation of the apoptotic signaling pathway. In addition, it decreased the Bcl-2 expression, leading to marked ovarian cancer cells sensitive to carboplatin by enhancing apoptosis. We then corroborated these results using in vivo experiments. Taken together, C. militaris inhibits carboplatin-resistant SKOV-3 cell proliferation and induces apoptosis possibly through ATF3/TP53 signaling upregulation and CHOP/PUMA activation. Therefore, our findings provide new insights into the treatment of carboplatin-resistant ovarian cancer using C. militaris.

Download Full-text

SMARCC1 Suppresses Tumor Progression by Inhibiting the PI3K/AKT Signaling Pathway in Prostate Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.678967 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhao-Ming Xiao ◽

Dao-Jun Lv ◽

Yu-zhong Yu ◽

Chong Wang ◽

Tao Xie ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Cycle Progression ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Transition ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

BackgroundSWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily C member 1 (SMARCC1) protein is a potential tumor suppressor in various cancers. However, its role in prostate cancer (PCa) remains controversial. The aim of this study was to determine the biological function of SMARCC1 in PCa and explore the underlying regulatory mechanisms.MethodsThe expression of SMARCC1 was validated in PCa tissues by immunohistochemistry. Meanwhile, function experiments were used to evaluate the regulatory role on cell proliferation and metastasis in PCa cells with SMARCC1 depletion both in vitro and in vivo. The expression levels of relevant proteins were detected by Western blotting.ResultsOur finding showed that SMARCC1 was significantly downregulated in prostate adenocarcinoma, with a higher Gleason score (GS) than that in low GS. The decreased expression of SMARCC1 was significantly correlated with a higher GS and poor prognosis. Additionally, we found that silencing of SMARCC1 dramatically accelerated cell proliferation by promoting cell cycle progression and enhancing cell migration by inducing epithelial mesenchymal transition (EMT). Furthermore, depletion of SMARCC1 facilitated PCa xenograft growth and lung metastasis in murine models. Mechanistically, the loss of SMARCC1 activated the PI3K/AKT pathway in PCa cells.ConclusionSMARCC1 suppresses PCa cell proliferation and metastasis via the PI3K/AKT signaling pathway and is a novel therapeutic target.

Download Full-text

HN1 Promotes Proliferation, Metastasis and Attenuates the Chemosensitivity of HCC Cells to Oxaliplatin by Inhibiting Degradation of HMGB1 Through Interacting With TRIM28

10.21203/rs.3.rs-754224/v1 ◽

2021 ◽

Author(s):

Ruhua Wang ◽

Yunong Fu ◽

Menglin Yao ◽

Xiaomeng Cui ◽

Yan Zhao ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Dna Lesions ◽

Advanced Hepatocellular Carcinoma ◽

Promoting Effect ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis ◽

Hcc Cells

Abstract Background: The oxaliplatin-based chemotherapy has revealed an encouraging therapeutic efficacy for advanced hepatocellular carcinoma patients. However, the development of resistance limits its clinical utilization. In addition, the chemotherapy resistance in HCC is usually accompanied with other malignant phenotypes, such as cell proliferation and metastasis, which together result in poor prognosis of HCC patients. Therefore, efforts should be made to explore potential regulators which fuel multiple events of HCC progression.Methods: The qRT-PCR, western blot, immunohistochemistry and immunofluorescence were performed to measure mRNA and protein expression. MTT assay, colony formation and Transwell assay were performed to evaluate cell proliferation and metastasis. Flow cytometry was performed to test cell apoptosis. Alkaline Comet assay was performed to measure DNA lesions. Transmission electron microscope analysis provided potent testimony of autophagy. The role of HN1 on the malignant phenotypes of hepatoma carcinoma was demonstrated in vitro and in vivo.Results: The immunohistochemistry analysis of HCC patient tissues revealed that the expression of HN1 was higher in HCC tissues compared to adjacent tissues and was associated with worse prognosis. In vitro, HN1 knockdown inhibited proliferation and metastasis of HCC cells, whereas HN1 overexpression promoted their proliferation and metastasis. In addition, we found that HN1 knockdown sensitized HCC cells to oxaliplatin, which is companied with deteriorated DNA damage and increased cell apoptosis in oxaliplatin-treated HCC cells. In vivo, HN1 knockdown inhibited the tumor growth and metastasis, and promoted the anti-cancer efficiency of oxaliplatin. Mechanically, HN1 prevented HMGB1 from ubiquitination and degradation via autophagy-lysosome pathway, which is related to its interaction with TRIM28, and overexpression of HMGB1 can restore the malignant phenotypes of HN1 knockdown in HCC cells. Furthermore, we found that HN1 can regulate cellular autophagy via HMGB1, which is important to tumor-promoting effect of HN1.Conclusions: In conclusion, we systemically revealed the multiple functions of HN1 in HCC progression and the underlying molecular mechanism, which indicated that HN1 could be a promising therapeutic target for HCC treatment.

Download Full-text

WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

10.21203/rs.3.rs-18963/v2 ◽

2020 ◽

Author(s):

Zi-Qing Shi ◽

Zi-Yan Chen ◽

Yao Han ◽

Heng-Yan Zhu ◽

Meng-Dan Lyu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Extracellular Signal ◽

And Migration

Abstract Background: Wnt-inducible signaling pathway protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on the proliferation and migration of ovarian cancer cells in vitro and in vivo.Results: Immunohistochemistry and western blotting indicated that WISP2 was highly expressed in various ovarian cancer tissues and cell lines，but weakly expressed in normal ovary tissue. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells while promoting cell apoptosis and affecting the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of phosphorylated extracellular signal-related kinase (p-ERK)1/2, as well as CCAAT/enhancer-binding protein α (CEBPα) and CEPBβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP).Conclusion: WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

Download Full-text

WISP2 promotes cell proliferation via targeting ERK and YAP in ovarian cancer cells

10.21203/rs.3.rs-18963/v1 ◽

2020 ◽

Author(s):

Zi-Qing Shi ◽

Zi-Yan Chen ◽

Yao Han ◽

Heng-Yan Zhu ◽

Meng-Dan Lyu ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Inhibitory Effect ◽

Ovarian Cancer Cells ◽

Growth Inhibitory ◽

Extracellular Signal ◽

And Migration

Abstract Background Wnt inducible signaling protein 2 (WISP2) is a wnt1-induced signaling pathway protein 2. Although studies indicate that WISP2 may promote the development of various tumors, its role in ovarian cancer remains unclear. The objective of the current study was to analyze the effects of WISP2 on proliferation and migration of ovarian cancer cells in vitro and in vivo . Results Immunohistochemistry and western blot results indicated that WISP2 was highly expressed in various ovarian tissues and cell lines. WISP2 deletion inhibited cell growth, clone formation, and migration of ovarian cancer cells. WISP2 deletion promoted cell apoptosis and affected the cell cycle. This growth inhibitory effect caused by WISP2 loss is due to the inhibition of extracellular signal-related kinase (p-ERK)1/2, as well as CEBPα and CEBPβ. In addition, WISP2 deletion also activated the Yes-associated protein (YAP). Conclusion WISP2 deletion inhibits ovarian cancer cell proliferation by affecting ERK signaling pathways.

Download Full-text

miRNA-148b suppresses hepatic cancer stem cell by targeting neuropilin-1

Bioscience Reports ◽

10.1042/bsr20150084 ◽

2015 ◽

Vol 35 (4) ◽

Cited By ~ 31

Author(s):

Qinying Liu ◽

Yangmei Xu ◽

Shenghong Wei ◽

Wei Gao ◽

Li Chen ◽

...

Keyword(s):

Stem Cells ◽

Cell Proliferation ◽

Stem Cell ◽

Therapeutic Strategy ◽

Hepatic Cancer ◽

Neuropilin 1 ◽

Proliferation And Metastasis ◽

Cell Proliferation And Metastasis

Our study revealed that miR-148b was specifically down-regulated in hepatic cancer stem cells (HCSCs) and affected cell proliferation and metastasis in vitro and tumorigenicity in vivo by directly targeting to Neuropilin-1(NRP-1), a transmembrane co-receptor involved in metastasis, suggesting that enforced miR-148b expression might be an efficient therapeutic strategy to eradicate HCSCs and reduce metastasis.

Download Full-text