scholarly journals Cullin-1 Regulates MG63 Cell Proliferation and Metastasis and is a Novel Prognostic Marker of Osteosarcoma

2017 ◽  
Vol 32 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Qinghua Cheng ◽  
Guoyong Yin
Keyword(s):  
Cell Proliferation ◽  
Mg63 Cell ◽  
Osteosarcoma Cell ◽  
Mmp9 Expression ◽  
Proliferation And Metastasis ◽  
Reliable Marker ◽  
Proliferation In Vitro

Background There is no reliable marker available for early detection, diagnostic confirmation or disease prognosis of osteosarcoma. Cullin-1 (CUL1) is a newly reported tumor-related gene, and we aimed to unravel its role in osteosarcoma. Methods We used immunohistochemistry to analyze the correlation between CUL1 expression and clinicopathological variables and patient survival. To evaluate the function of CUL1, a group of 28 osteosarcoma patients were recruited for this study. The role of regulation of CUL1 in osteosarcoma was studied in vitro and in vivo. In addition, we further investigated the signaling pathway of CUL1 in osteosarcoma progression. Results We first discovered that CUL1 expression was up-regulated in human osteosarcoma tissues and inversely correlated with osteosarcoma differentiation. In addition, CUL1 promotes osteosarcoma cell proliferation in vitro and in vivo. We also found that CUL1 promotes osteosarcoma cell invasion and metastasis in vitro and in vivo. High levels of CUL1 promote osteosarcoma progression via up-regulation of MMP9 expression. Conclusions Our results demonstrate that increased CUL1 expression is significantly correlated with poor prognosis of patients with osteosarcoma. CUL1 might be an important marker and a therapeutic target for osteosarcoma.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

scholarly journals HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fengjie Jiang ◽  
Xiaozhu Tang ◽  
Chao Tang ◽  
Zhen Hua ◽  
Mengying Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
The Stability ◽  
Induced Apoptosis ◽  
Proliferation In Vitro

AbstractN6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

scholarly journals MiR-155-5p suppresses SOX1 to promote proliferation of cholangiocarcinoma via RAF/MEK/ERK pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Close Relation ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro

Abstract Background Accumulating evidence has demonstrated the close relation of SOX1 with tumorigenesis and tumor progression. Upregulation of SOX1 was recently shown to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) is not well characterized. Methods Expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined using public GEO database. Western blot and immunohistochemistry were used to confirm the expression levels. Cell proliferation assay (CCK-8) and colony formation assay were performed to assess proliferation of CCA cells. A mouse model of subcutaneous transplantable tumors was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were determined using Targetscan and dual-luciferase reporter assay. Results SOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and suppressed tumor growth in vivo. miR-155-5p directly targeted the 3′-untranslated region (3′UTR) of SOX1 and inhibited expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation, and thus CCA proliferation. However, restoration of SOX1 expression in miR-155-5p overexpressing cell lines decreased the phosphorylation level of RAF, MEK and ERK, as well as the proliferation of CCA cells. Conclusion MiR-155-5p decreased the expression of SOX1 by binding to its 3′UTR, which activated the RAF/MEK/ERK signaling pathway and promoted CCA progression.

scholarly journals LncRNA RBM5-AS1 Promotes Osteosarcoma Cell Proliferation, Migration, and Invasion

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Biyong Deng ◽  
Runsang Pan ◽  
Xin Ou ◽  
Taizhe Wang ◽  
Weiguo Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Western Blotting ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Pediatric Age Group ◽  
The Relationship

Purpose. Osteosarcoma (Os) is the most frequent malignant tumor of the bone in the pediatric age group, and accumulating evidences show that lncRNAs play a key role in the development of Os. Thus, we investigated the role of RBM5-AS1 and its molecular mechanism. Methods. The expression of RBM5-AS1 in Os tissues and cell lines was detected by real-time polymerase chain reaction (QPCR). The effect of RBM5-AS1 on the proliferation of Os cells was detected using CCK8 assays and flow cytometry. The effect of RBM5-AS1 on the migration and invasion of Os cells was detected by transwell assays. And we performed QPCR and western blotting assays to investigate the relationship between RBM5-AS1 and RBM5. Finally, western blotting assays were performed to explore the mechanism of RBM5. Results. LncRNA RBM5-AS1 was overexpressed in the Os tissues and cell lines. And lncRNA RBM5-AS1 promoted Os cell proliferation, migration, and invasion in vitro and tumor growth in vivo. LncRNA RBM5-AS1 targets RBM5 in Os cells. Conclusion. To sum up, the results showed that lncRNA RBM5-AS1 promotes cell proliferation, migration, and invasion in Os.

scholarly journals MiR-155-5p Suppress SOX1 to Promote the Proliferation of Cholangiocarcinoma via RAF/MEK/ERK Pathway

2021 ◽  
Author(s):  
Da Wang ◽  
Fei Xiong ◽  
Guanhua Wu ◽  
Wenzheng Liu ◽  
Bing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Phosphorylation Level ◽  
Erk Phosphorylation ◽  
Overexpressing Cell ◽  
Proliferation In Vitro ◽  
Geo Database

Abstract BackgroundAccumulating evidences indicate that SOX1 is closely related to tumorigenesis and development, upregulation of SOX1 is recently reported to suppress growth of human cancers. However, the expression and role of SOX1 in cholangiocarcinoma (CCA) remain unknown.MethodsThe expression levels of SOX1 in CCA tissues and normal bile duct tissues were examined by public GEO database, and western blot and immunohistochemistry were used to confirm the expression again. Cell proliferation assay (CCK-8) and colony formation assay were performed to determine proliferation of CCA cells. A model of transplatable subcutaneously tumors in mouse was used to evaluated proliferation of CCA in vivo. The putative regulating factor of SOX1 were disclosed by Targetscan and a dual-luciferase reporter assay.ResultsSOX1 was downregulated in CCA tissues. Overexpression of SOX1 significantly inhibited cell proliferation in vitro and tumor growth in vivo. Furthermore, miR-155-5p directly targets 3’UTR of SOX1 and inhibits expression of SOX1, resulting in the activation of RAF, MEK and ERK phosphorylation and thus CCA proliferation. However, when SOX1 expression was restored in miR-155-5p overexpressing cell lines, the phosphorylation level of RAF, MEK and ERK were decreased, as well as the proliferation of CCA cells.ConclusionMiR-155-5p could bind to the 3’UTR of SOX1 to decrease the expression of SOX1, and further activated the RAF/MEK/ERK signaling pathway to promote CCA progression.

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.

scholarly journals Ethanol Impairs NRF2/Antioxidant and Growth Signaling in the Intact Placenta In Vivo and in Human Trophoblasts

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 669 ◽  
Author(s):  
Sambantham Shanmugam ◽  
Dhyanesh Patel ◽  
John M. Wolpert ◽  
Caezaan Keshvani ◽  
Xiaobo Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cyclin D1 ◽  
Developmental Toxicity ◽  
Ethanol Vapor ◽  
Proliferation Indices ◽  
Growth Promoting ◽  
Proliferation In Vitro

NRF2 is a redox-sensitive transcription factor that depending on the duration or magnitude of the stress, either translocates to the nucleus (beneficial) or is degraded in the cytosol (harmful). However, the role of NRF2-based mechanism(s) under ethanol (E)-induced developmental toxicity in the placental context remains unknown. Here, we used a rat prenatal model of maternal alcohol stress consisting of intermittent ethanol vapor (IEV) daily from GD11 to GD20 with a 6 h ON/18 h OFF in a vapor chamber and in vitro placental model consisting of HTR-8 trophoblasts exposed to 86 mM of E for either 24 h or 48 h. The role of NRF2 was evaluated through the NRF2-transactivation reporter assay, qRT-PCR, and Western blotting for NRF2 and cell growth-promoting protein, and cell proliferation assay. In utero and in vitro E decreased the nuclear NRF2 content and diminished its transactivation ability along with dysregulation of the proliferation indices, PCNA, CYCLIN-D1, and p21. This was associated with a ~50% reduction in cell proliferation in vitro in trophoblasts. Interestingly, this was found to be partially rescued by ectopic Nrf2 overexpression. These results indicate that ethanol-induced dysregulation of NRF2 coordinately regulates PCNA/CYCLIN-D1/p21 involving growth network, at least partially to set a stage for placental perturbations.

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