scholarly journals FAM49B promotes breast cancer proliferation, metastasis, and chemoresistance by stabilizing ELAVL1 protein and regulating downstream Rab10/TLR4 pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanhui Li ◽  
Yue Xiong ◽  
Zhen Wang ◽  
Jianjun Han ◽  
Sufang Shi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Mechanistic Studies ◽  
Gene Interaction Network ◽  
Kaplan Meier ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Breast cancer (BC) is one of the most common cancers and the leading cause of death in women. Previous studies have demonstrated that FAM49B is implicated in several tumor progression, however, the role and mechanism of FAM49B in BC remain to be explored. Therefore, in this study, we aimed to systematically study the role of FAM49B in the proliferation, metastasis, apoptosis, and chemoresistance of BC, as well as the corresponding molecular mechanisms and downstream target. Methods The ONCOMINE databases and Kaplan–Meier plotter databases were analyzed to find FAM49B and its prognostic values in BC. FAM49B expression in BC and adjacent non-tumor tissues was detected by western blot and IHC. Kaplan–Meier analysis was used to identify the prognosis of BC patients. After FAM49B knockdown in MCF-7 and MDA-MB-231 cells, a combination of co-immunoprecipitation, MTT, migration, and apoptosis assays, nude mouse xenograft tumor model, in addition to microarray detection and data analysis was used for further mechanistic studies. Results In BC, the results showed that the expression level of FAM49B was significantly higher than that in normal breast tissue, and highly expression of FAM49B was significantly positively correlated with tumor volume, histological grade, lymph node metastasis rate, and poor prognosis. Knockdown of FAM49B inhibited the proliferation and migration of BC cells in vitro and in vivo. Microarray analysis revealed that the Toll-like receptor signaling pathway was inhibited upon FAM49B knockdown. In addition, the gene interaction network and downstream protein validation of FAM49B revealed that FAM49B positively regulates BC cell proliferation and migration by promoting the Rab10/TLR4 pathway. Furthermore, endogenous FAM49B interacted with ELAVL1 and positively regulated Rab10 and TLR4 expression by stabilizing ELAVL1. Moreover, mechanistic studies indicated that the lack of FAM49B expression in BC cells conferred more sensitivity to anthracycline and increased cell apoptosis by downregulating the ELAVL1/Rab10/TLR4/NF-κB signaling pathway. Conclusion These results demonstrate that FAM49B functions as an oncogene in BC progression, and may provide a promising target for clinical diagnosis and therapy of BC.

scholarly journals MiR-612 Suppresses the Proliferation and Migration of Breast Cancer Cells and Induces their Apoptosis Through the AKT/ERK Signaling Cascade

2021 ◽  
Author(s):  
Sina Taefehshokr ◽  
Sahar Safaei ◽  
Amin Mahmoudpour ◽  
Ehsan Mikaeili ◽  
Mohammad Amini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Erk Signaling ◽  
Cycle Arrest ◽  
Exact Function ◽  
And Migration ◽  
Proliferation And Migration

Abstract MicroRNAs (miRs) as non-coding RNAs have been generating widespread interest in cancer diagnosis and treatment. Among the previously studied miRs, miR-612 has been addressed to have a tumor suppressor function in all types of the studied cancers except esophageal squamous cell carcinoma. Despite this interest, the exact function of miR-612 in breast cancer (BC) remains elusive. Within the framework of these criteria, we tried to study the role of miR-612 in BC development. The human BC cell lines, MDA-MB-231 and MDA-MB-468 were transfected with miR-612. The effects of miR-612 replacement on viability, migration, invasion, cell cycle, apoptosis, and colony formation were studied in vitro. Furthermore, the protein expression of AKT and ERK were evaluated by Western blotting analysis. The results indicated that miR-612 decreased cell viability, migration, invasion, and colony formation of BC cells. Moreover, apoptosis was augmented, and thus cell cycle arrest was induced. Also, miR-612 decreased the expression and phosphorylation of proteins of the AKT/ERK signaling pathway. We suggest that miR-612-related stimulatory effects on apoptosis and its inhibitory impacts on proliferation and migration of BC cells mediates partly by suppressing the AKT/ERK signaling pathway.

scholarly journals The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/β-catenin Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Chun Tang ◽  
Xuehui Wang ◽  
Changle Ji ◽  
Wenfang Zheng ◽  
Yunhe Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Signaling Pathway ◽  
Opposite Effect ◽  
Novel Targets ◽  
And Migration ◽  
Proliferation And Migration

In this study, we demonstrated that miR-640 is significantly downregulated in breast cancer (BC) tissues and cell lines. Overexpression of miR-640 inhibited the proliferation and migration of BC in vitro and in vivo, while depletion of miR-640 exhibited the opposite effect. Importantly, miR-640 could directly target Wnt7b, thereby regulating Wnt/β-catenin signaling pathway in BC. In conclusion, miR-640/Wnt7b suppresses BC cells tumorigenesis via Wnt/β-catenin signaling pathway, which might be novel targets for BC targeted therapy.

scholarly journals Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhenghui Cheng ◽  
Yawen Zhang ◽  
Yinchao Tian ◽  
Yuhan Chen ◽  
Fei Ding ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Peripheral Nerves ◽  
Molecular Mechanisms ◽  
Αvβ3 Integrin ◽  
Promoting Effect ◽  
Ccn Family ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

scholarly journals miR-3188 Regulates Cell Proliferation, Apoptosis, and Migration in Breast Cancer by Targeting TUSC5 and Regulating the p38 MAPK Signaling Pathway

2018 ◽  
Vol 26 (3) ◽  
pp. 363-372 ◽  
Author(s):  
Xiaowen Chen ◽  
Jianli Chen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
And Migration ◽  
Mcf 7

This study intended to investigate the effects of miR-3188 on breast cancer and to reveal the possible molecular mechanisms. miR-3188 was upregulated and TUSC5 was downregulated in breast cancer tissues and MCF-7 cells compared to normal tissue and MCF-10 cells. After MCF-7 cells were transfected with miR-3188 inhibitor, cell proliferation and migration were inhibited, whereas apoptosis was promoted. Luciferase reporter assay suggested that TUSC5 was a target gene of miR-3188. In addition, miR-3188 overexpression increased the p-p38 expression, while miR-3188 suppression decreased the p-p38 expression significantly. miR-3188 regulated breast cancer progression via the p38 MAPK signaling pathway. In conclusion, miR-3188 affects breast cancer cell proliferation, apoptosis, and migration by targeting TUSC5 and activating the p38 MAPK signaling pathway. miR-3188 may serve as a potential therapeutic agent for the treatment of breast cancer.

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 CCR2 Expression Promotes Diffuse Large B Lymphoma Cell Survival and Invasion

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4494-4494
Author(s):  
Li Yan-Li ◽  
Quan-Quan Hu ◽  
Zhao-Feng Wen ◽  
Qian Li ◽  
Zhi-Min Zhai
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cc Chemokine ◽  
Ccr2 Expression ◽  
And Migration ◽  
Ccr2 Antagonist ◽  
Proliferation And Migration

Abstract Objective: Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma world wide. It is a phenotypically and genetically heterogeneous disease, accounting for 30-40% of all cases. 50%-70% of patients can be cured by the R-CHOP regimen, but nearly one-third of patients develop relapsed or refractory disease. CC chemokine receptor 2 (CCR2), the high affinity receptor of CC-Chemokine Ligand 2 (CCL2), which is the most representative of the CC chemokine family members, has be regarded to involve in tumor growth, angiogenesis, epithelial mesenchymal transition, metastasis and immune escape etc.. In recent years, the role and mechanism in DLBCL has not been reported yet. Our preliminary study showed that high expression of CCR2 was correlated with clinicopathological characteristics, and an adverse prognostic factor for overall survival (OS) and progression-free survival (PFS) of DLBCL patients. The purpose of this study is to investigate the role of CCR2 expression in DLBCL cells proliferation and migration by in vitro and in vivo. Methods: CCR2 expression were analyzed in human DLBCL cell lines (SUDHL-2, SUDHL-4, SUDHL-6, OCI-Ly8 and OCI-Ly10) by Western blot (WB). SUDHL-2 and OCI-Ly8 cells were incubated with CCR2 antagonist SC-202525 (Santa Crutz Biotechnology), and control cells were left untreated. The proliferation, migration, apoptosis and signaling pathway were detected by CCK8, transwell, flow cytometry (FC) and WB, respectively in vitro. The engraftment, tumor growth, dissemination and survival time were observed in BALB/c nude mice. Results: CCR2 were expressed in all human DLBCL cell lines (relative CCR2 expression was higher in SUDHL-2, SUDHL-4 and OCI-Ly8 than in SUDHL-6 and OCI-Ly10 cell lines). Blockade of CCR2 expression signaling with CCR2 antagonist inhibited tumor cell proliferation, migration and anti-apoptosis ability. The signaling involved in the proliferation and migration of DLBCL cells by activating PI3K/Akt signaling pathway, and induced apoptosis through activation of P38MARK signaling pathway. Expression of CCR2 was also associated with increased engraftment, tumor growth and dissemination, and decreased survival time in xenograft mice. Furthermore, administration of CCR2 antagonist decreased tumor growth and dissemination of DLBCL cells, and increased survival time in the xenograft model. Conclusions: Our study demonstrates that CCR2 plays an important role in the development of DLBCL by stimulating cell proliferation, migration and anti-apoptosis. The inhibition of CCR2 may, therefore, be a potential target for anticancer therapy in DLBCL. Disclosures No relevant conflicts of interest to declare.

scholarly journals BCKDK Promotes Epithelial Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway

2021 ◽  
Author(s):  
Huashun Li ◽  
Dongyang Yu ◽  
Lianbing Li ◽  
Juanjuan Xiao ◽  
Yijian Zhu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Cell Transformation ◽  
Gynecologic Cancer ◽  
Erk Signaling ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Ovarian cancer is the most fatal gynecologic cancer, and epithelial ovarian cancer (EOC) is the most common type. The branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in many serious human diseases, including cancers. Its function in promoting cell proliferation and migration has been reported in various cancers. However, the biological role of BCKDK and its molecular mechanisms underlying EOC initiation and progression are unclear.Methods: First, the expression level of BCKDK in EOC cell lines or tissues was determined using tissue microarray (TMA)-based immunohistochemistry or western blotting. Then, growth curve analysis, anchorage-independent cell transformation assays, wound healing assays, cell migration assays, and tumor xenografts were used to test whether BCKDK could promote cell transformation or metastasis. Finally, the signaling pathways involved in this process were investigated by western blotting or immunoprecipitation.Results: We found that the expression of BCKDK was upregulated in EOC tissues and that high expression of BCKDK was correlated with an advanced pathological grade in patients. The ectopic overexpression of BCKDK promoted the proliferation and migration of EOC cells, and the knockdown of BCKDK with shRNAs inhibited the proliferation and migration of EOC ex vivo and in vivo. Moreover, BCKDK promoted EOC proliferation and migration by activating MEK.Conclusions: Our results demonstrate that BCKDK promotes EOC proliferation and migration by activating the MEK/ERK signaling pathway. Targeting the BCKDK-MEK axis may provide a new therapeutic strategy for treating patients with EOC.

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