scholarly journals Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo

2017 ◽  
Vol Volume 10 ◽  
pp. 5873-5882 ◽  
Author(s):  
Yan Dong ◽  
Cai Chang ◽  
Jingtian Liu ◽  
Jinwei Qiang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

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

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.

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

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.

scholarly journals TMEM176B Regulates AKT/mTOR Signaling and Tumor Growth in Triple-Negative Breast Cancer

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3430
Author(s):  
Chifei Kang ◽  
Ran Rostoker ◽  
Sarit Ben-Shumel ◽  
Rola Rashed ◽  
James Andrew Duty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
And Migration ◽  
Proliferation And Migration

TMEM176B is a member of the membrane spanning 4-domains (MS4) family of transmembrane proteins, and a putative ion channel that is expressed in immune cells and certain cancers. We aimed to understand the role of TMEM176B in cancer cell signaling, gene expression, cell proliferation, and migration in vitro, as well as tumor growth in vivo. We generated breast cancer cell lines with overexpressed and silenced TMEM176B, and a therapeutic antibody targeting TMEM176B. Proliferation and migration assays were performed in vitro, and tumor growth was evaluated in vivo. We performed gene expression and Western blot analyses to identify the most differentially regulated genes and signaling pathways in cells with TMEM176B overexpression and silencing. Silencing TMEM176B or inhibiting it with a therapeutic antibody impaired cell proliferation, while overexpression increased proliferation in vitro. Syngeneic and xenograft tumor studies revealed the attenuated growth of tumors with TMEM176B gene silencing compared with controls. We found that the AKT/mTOR signaling pathway was activated or repressed in cells overexpressing or silenced for TMEM176B, respectively. Overall, our results suggest that TMEM176B expression in breast cancer cells regulates key signaling pathways and genes that contribute to cancer cell growth and progression, and is a potential target for therapeutic antibodies.

scholarly journals GRHL3 Promotes Tumor Growth and Metastasis via the MEK Pathway in Colorectal Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Lin Tan ◽  
Weiming Qu ◽  
Dajun Wu ◽  
Minji Liu ◽  
Qian Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Underlying Mechanism ◽  
Promoting Effect ◽  
Promote Tumor Growth ◽  
Proliferation And Metastasis ◽  
Tumor Growth And Metastasis ◽  
Cell Proliferation And Metastasis

GRHL3 is a factor associated with a tumor, of which the molecular mechanism remains a further investigation. We explored the underlying mechanism of tumor-promoting effect of GRHL3 in colorectal cancer (CRC), which is involved in the MEK1/2 pathway. The expression of GRHL3 was measured in CRC and adjacent normal tissue using qPCR and immunohistochemical staining. Lentivirus-mediated knockdown expression of GRHL3 was performed in the CRC cell line HT29. Cell proliferation and metastasis were assayed in vitro, and tumorigenicity was investigated in vivo. We found higher GRHL3 expression in colorectal cancer, which was negatively correlated with patients’ prognosis. Results from studies in vitro and in vivo indicated that downregulation of GRHL3 expression inhibited tumor growth and metastasis and inhibited the activation of the MEK1/2 pathway. The effect of GRHL3 downexpression was the same as that of MEK1/2 antagonists on suppression of tumor growth and metastasis. Our results suggested that GRHL3 may act as an oncogene to promote tumor growth and metastasis via the MEK pathway in colorectal cancer.

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

2015 ◽  
Vol 35 (4) ◽  
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.

scholarly journals Andrographolide Suppresses the Growth and Metastasis of Luminal-Like Breast Cancer by Inhibiting the NF-κB/miR-21-5p/PDCD4 Signaling Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Junchen Li ◽  
Lixun Huang ◽  
Zinan He ◽  
Minggui Chen ◽  
Yi Ding ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Antitumor Agent ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Tumor Growth And Metastasis

Tumor growth and metastasis are responsible for breast cancer-related mortality. Andrographolide (Andro) is a traditional anti-inflammatory drug used in the clinic that inhibits NF-κB activation. Recently, Andro has been found in the treatment of various cancers. Andro inhibits breast cell proliferation and invasion and induces apoptosis via activating various signaling pathways. Therefore, the underlying mechanisms with regard to the antitumor effects of Andro still need to be further confirmed. Herein, a MMTV-PyMT spontaneous luminal-like breast cancer lung metastatic transgenic tumor model was employed to estimate the antitumor effects of Andro on breast cancer in vivo. Andro significantly inhibited tumor growth and metastasis in MMTV-PyMT mice and suppressed the cell proliferation, migration, and invasion of MCF-7 breast cancer cells in vitro. Meanwhile, Andro significantly inhibited the expression of NF-κB, and the downregulated NF-κB reduced miR-21-5p expression. In addition, miR-21-5p dramatically inhibited the target gene expression of programmed cell death protein 4 (PDCD4). In the current study, we demonstrated the potential anticancer effects of Andro on luminal-like breast cancer and indicated that Andro inhibits the expression of miR-21-5p and further promotes PDCD4 via NF-κB suppression. Therefore, Andro could be an antitumor agent for the treatment of luminal-like breast cancer in the clinic.

scholarly journals Semaphorin 4D promotes the proliferation and metastasis of bladder cancer by activating the PI3K/AKT pathway

2019 ◽  
Vol 105 (3) ◽  
pp. 231-242 ◽  
Author(s):  
Jian-jun Lu ◽  
Yao-wu Su ◽  
Chao-jun Wang ◽  
Di-feng Li ◽  
Liang Zhou
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Cell ◽  
Bladder Cancer Cell ◽  
Akt Pathway ◽  
Semaphorin 4D ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial–mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway.

Accumulation of AGO2 facilitates tumor proliferation and metastasis through upregulating Survivin, Vimentin and Snail in human hepatocellular carcinoma

2019 ◽  
Author(s):  
Yang Yang ◽  
Qi Mei
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Xenograft Model ◽  
Proliferation And Metastasis ◽  
Interfering Rna ◽  
Cell Proliferation And Metastasis

Abstract Background：Argonaute 2 (AGO2), a typical member of the Ago gene family, plays a pivotal role in hepatocellular carcinoma (HCC) tumorgenesis through regulating the short interfering RNA-mediated gene silencing. However, the underlined mechanism needs clarified. Herein, we found that AGO2 was frequently upregulated in human HCC cancerous tissues compared with non-cancerous tissues. Methods: Clinical analyses were performed to determine the relation between the expression level of AGO2 and prognosis in HCC patients. By using CRISPR/Cas9 approach in SMMC-7721 cells and establishing xenograft model in nude mice, we further identified the role of AGO2 in HCC. Gene expression microarray analysis was used to reveal the changes of gene expression profile mediated by AGO2 depletion in SMMC-7721 cells. Results: We observed that the overexpression of AGO2 was associated with poor prognosis in HCC patients. The knockout of AGO2 inhibited tumor cell proliferation and metastasis in vivo and in vitro. We also identified that AGO2 facilitates HCC tumorigenesis through modulating Survivin, Vimentin and Snail expression. Conclusions: Therefore, this study not only demonstrates that accumulation of AGO2 promotes cell proliferation and metastasis in HCC, but also provides a novel molecular mechanism in HCC progression.

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