scholarly journals PUMILIO Proteins in Colorectal Cancer: Tumor Growth Promoting Function and Potential as Therapeutic Targets

2021 ◽  
Author(s):  
Yuanyuan Gong ◽  
Zukai Liu ◽  
Yihang Yuan ◽  
Zhenzhen Yang ◽  
Jiawei Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Therapeutic Targets ◽  
Cancer Models ◽  
Cancer Tumor ◽  
Direct Target ◽  
Growth Promoting ◽  
Pumilio Proteins ◽  
Puf Family

Abstract PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under explored. Here, we found that the expression of Pum1 and Pum2 are increased in clinical colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 significantly inhibited the progression of colitis associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 resulted in a significant decrease in the tumorigenicity. In addition, delayed G1/S transition was observed. We identified p21/Cdkn1a as direct target of PUM1, and abrogation of the PUM1 binding site in p21 resulted in decreased tumor cell growth as well as delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduced colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal a tumor growth promoting role of PUM proteins in CRC and its potential as therapeutic targets.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

scholarly journals Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Chunyu Zhang ◽  
Pan Liu ◽  
Jiaming Huang ◽  
Yuandong Liao ◽  
Chaoyun Pan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Tumor Growth ◽  
Poor Prognosis ◽  
Prognostic Biomarker ◽  
Circular Rna ◽  
Circular Rnas ◽  
Inhibit Tumor Growth ◽  
Cancer Tumor ◽  
Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

scholarly journals Tumor-growth–promoting cyclooxygenase-2 prostaglandin E2 pathway provides medulloblastoma therapeutic targets

2008 ◽  
Vol 10 (5) ◽  
pp. 661-674 ◽  
Author(s):  
Ninib Baryawno ◽  
Baldur Sveinbjörnsson ◽  
Staffan Eksborg ◽  
Abiel Orrego ◽  
Lova Segerström ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Prostaglandin E2 ◽  
Therapeutic Targets ◽  
Cyclooxygenase 2 ◽  
Growth Promoting

scholarly journals Arginase-1+ Exosomes from Reprogrammed Macrophages Promote Glioblastoma Progression

2020 ◽  
Vol 21 (11) ◽  
pp. 3990 ◽  
Author(s):  
Juliana H. Azambuja ◽  
Nils Ludwig ◽  
Saigopalakrishna S. Yerneni ◽  
Elizandra Braganhol ◽  
Theresa L. Whiteside
Keyword(s):  
Tumor Growth ◽  
In Vitro Model ◽  
Potential Therapeutic Target ◽  
Tumor Cell Migration ◽  
Arginase 1 ◽  
Growth Promoting ◽  
Vitro Model ◽  
Cell Migration And Proliferation

Interactions between tumor cells and tumor-associated macrophages (TAMs) are critical for glioblastoma progression. The TAMs represent up to 30% of the glioblastoma mass. The role of TAMs in tumor progression and in the mechanisms underlying tumor growth remain unclear. Using an in vitro model resembling the crosstalk between macrophages and glioblastoma cells, we show that glioblastoma-derived exosomes (GBex) reprogram M1 (mediate pro-inflammatory function) and M2 (mediate anti-inflammatory function) macrophages, converting M1 into TAMs and augmenting pro-tumor functions of M2 macrophages. In turn, these GBex-reprogrammed TAMs, produce exosomes decorated by immunosuppressive and tumor-growth promoting proteins. TAM-derived exosomes disseminate these proteins in the tumor microenvironment (TME) promoting tumor cell migration and proliferation. Mechanisms underlying the promotion of glioblastoma growth involved Arginase-1+ exosomes produced by the reprogrammed TAMs. A selective Arginase-1 inhibitor, nor-NOHA reversed growth-promoting effects of Arginase-1 carried by TAM-derived exosomes. The data suggest that GBex-reprogrammed Arginase-1+ TAMs emerge as a major source of exosomes promoting tumor growth and as a potential therapeutic target in glioblastoma.

scholarly journals GH and IGF System: The Regulatory Role of miRNAs and lncRNAs in Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Cecilia Catellani ◽  
Gloria Ravegnini ◽  
Chiara Sartori ◽  
Sabrina Angelini ◽  
Maria E. Street
Keyword(s):  
Colorectal Cancer ◽  
Pituitary Adenomas ◽  
Biological Processes ◽  
Intracranial Tumors ◽  
Regulate Gene Expression ◽  
Gh Secretion ◽  
Igf System ◽  
Non Coding Rnas ◽  
Growth Promoting

Growth hormone (GH) and the insulin-like growth factor (IGF) system are involved in many biological processes and have growth-promoting actions regulating cell proliferation, differentiation, apoptosis and angiogenesis. A recent chapter in epigenetics is represented by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) which regulate gene expression. Dysregulated miRNAs and lncRNAs have been associated with several diseases including cancer. Herein we report the most recent findings concerning miRNAs and lncRNAs regulating GH and the IGF system in the context of pituitary adenomas, osteosarcoma and colorectal cancer, shedding light on new possible therapeutic targets. Pituitary adenomas are increasingly common intracranial tumors and somatotroph adenomas determine supra-physiological GH secretion and cause acromegaly. Osteosarcoma is the most frequent bone tumor in children and adolescents and was reported in adults who were treated with GH in childhood. Colorectal cancer is the third cancer in the world and has a higher prevalence in acromegalic patients.

The lymphangiogenic factor CCBE1 promotes angiogenesis and tumor growth in colorectal cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Wenjun Ding ◽  
Wenfang Tang ◽  
Jiajun Zhi
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Calcium Binding ◽  
Umbilical Vein ◽  
Colorectal Cancer Cell Line ◽  
Vascular Endothelial ◽  
Factor C

Background: Collagen and calcium-binding EGF domain-1 (CCBE1) is essential for the development of the lymphatic vasculature and colorectal cancer (CRC) lymphangiogenesis as it enhances the proteolytic process of vascular endothelial growth factor C (VEGFC) activating VEGFR3. The fully processed mature VEGFC could also activate VEGFR2, the important endothelial-specific receptor tyrosine kinase, involved in blood vascular development and tumor angiogenesis. However, the role of CCBE1 in cancer angiogenesis remains undefined. Methods: In this paper, we find that the protein expression of CCBE1 is higher in the primary CRC tissue with distant metastasis and positively correlated with blood vessel density. Results: The mRNA expression of CCBE1 is closely positively correlated with the vascular endothelial marker CD31 and VEGFR2 in CRC from TCGA datasets. The supernatant of the colorectal cancer cell line HCT116 with CCBE1 overexpression significantly promotes the tube formation ability of the human umbilical vein endothelial cells (HUVECs) in vitro and enhances angiogenesis and tumor growth in vivo. Knockdown of CCBE1 decreases the angiogenic ability of CRC. Conclusion: Our results demonstrate the angiogenic role of CCBE1 in CRC.

scholarly journals The CCR2/MCP-1 Chemokine Pathway and Lung Adenocarcinoma

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3723
Author(s):  
Payal Mittal ◽  
Liqing Wang ◽  
Tatiana Akimova ◽  
Craig A. Leach ◽  
Jose C. Clemente ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Suppressor Cells ◽  
Treg Cells ◽  
Cancer Models ◽  
Inflammatory Site ◽  
Ccr2 Antagonist

Host anti-tumor immunity can be hindered by various mechanisms present within the tumor microenvironment, including the actions of myeloid-derived suppressor cells (MDSCs). We investigated the role of the CCR2/MCP-1 pathway in MDSC-associated tumor progression in murine lung cancer models. Phenotypic profiling revealed maximal expression of CCR2 by tumor-resident MDSCs, and MCP-1 by transplanted TC1 tumor cells, respectively. Use of CCR2-knockout (CCR2-KO) mice showed dependence of tumor growth on CCR2 signaling. Tumors in CCR2-KO mice had fewer CCR2low MDSCs, CD4 T cells and Tregs than WT mice, and increased infiltration by CD8 T cells producing IFN-γ and granzyme-B. Effects were MDSC specific, since WT and CCR2-KO conventional T (Tcon) cells had comparable proliferation and production of inflammatory cytokines, and suppressive functions of WT and CCR2-KO Foxp3+ Treg cells were also similar. We used a thioglycolate-induced peritonitis model to demonstrate a role for CCR2/MCP-1 in trafficking of CCR2+ cells to an inflammatory site, and showed the ability of a CCR2 antagonist to inhibit such trafficking. Use of this CCR2 antagonist promoted anti-tumor immunity and limited tumor growth. In summary, tumor cells are the prime source of MCP-1 that promotes MDSC recruitment, and our genetic and pharmacologic data demonstrate that CCR2 targeting may be an important component of cancer immunotherapy.

scholarly journals Role of p21-activated kinase (PAK) in K-RAS mutant human colorectal cancer models

2018 ◽  
Vol 29 ◽  
pp. iii16
Author(s):  
R.C. Orsini ◽  
V. D'Amato ◽  
R. Rosa ◽  
C. Di Mauro ◽  
P. Ciciola ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Human Colorectal Cancer ◽  
Cancer Models ◽  
P21 Activated Kinase

scholarly journals MicroRNA-30a-5p-Mediated Autophagy Regulates Formation of Foam Cells from THP-1-derived Macrophages

2021 ◽  
Author(s):  
Chunhui Geng ◽  
Chao Wang ◽  
Guangming Su ◽  
Shengjiao Wang ◽  
Jiashan Li ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Foam Cells ◽  
Pathological Process ◽  
Inflammatory Factors ◽  
Growth Promoting ◽  
The Relationship ◽  
Accumulation Of Lipids ◽  
Progression Of Atherosclerosis

Abstract MicroRNAs are widely considered to be involved in the pathogenesis of atherosclerosis. Whereas the importance of miR-30a-5p as a tumor growth-promoting factor has been extensively studied, the relationship between this particular microRNA and atherosclerosis remains to be clarified. In this study, the role of miR-30a-5p in the formation of foam cells from THP-1-derived macrophages was investigated. It was found that miR-30a-5p could robustly regulate the pathological process of atherosclerosis by inhibiting autophagy and increasing the accumulation of lipids, the expression of inflammatory factors, and the apoptosis of macrophages. These results provide guidance for future assessments of the progression of atherosclerosis and for the development of intervention targets for the treatment of this disease.

scholarly journals circAPLP2 promotes colorectal cancer progression by upregulating HELLS by targeting miR-335-5p

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 338-350
Author(s):  
Rui Xiang ◽  
Min Feng ◽  
Xin Zhou ◽  
Lihong Ma ◽  
Ningfei Dong
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Tumor Growth ◽  
Nude Mice ◽  
Solid Tumor ◽  
Cell Apoptosis ◽  
Colony Formation ◽  
Cell Cycle Progression ◽  
Cycle Progression

Abstract Background Colorectal cancer (CRC) is one of the deadliest cancers in the world. Increasing evidence suggests that circular RNAs (circRNAs) are implicated in CRC pathogenesis. This study aimed to determine the role of circAPLP2 and explore a potential mechanism of circAPLP2 action in CRC. Methods The expression of circAPLP2, miR-335-5p and helicase lymphoid-specific (HELLS) mRNA in CRC tissues and cells was measured by quantitative real-time polymerase chain reaction (qPCR). The functional effects of circAPLP2 on cell cycle progression/cell apoptosis, colony formation, cell migration, invasion and glycolysis metabolism were investigated by flow cytometry assay, colony formation assay, wound healing assay, transwell assay and glycolysis stress test. Glycolysis metabolism was also assessed by the levels of glucose uptake and lactate production. The protein levels of HELLS and HK2 were detected by western blot. The interaction between circAPLP2 and miR-335-5p, or miR-335-5p and HELLS was verified by dual-luciferase reporter assay. The role of circAPLP2 on solid tumor growth in nude mice was investigated. Results circAPLP2 and HELLS were overexpressed, but miR-335-5p was downregulated in CRC tissues and cells. Functional analyses showed that circAPLP2 knockdown suppressed CRC cell cycle progression, colony formation, migration, invasion and glycolysis metabolism, induced cell apoptosis and blocked solid tumor growth in nude mice. Moreover, miR-335-5p was a target of circAPLP2, and miR-335-5p could also bind to HELLS. Rescue experiments presented that miR-335-5p inhibition reversed the effects of circAPLP2 knockdown, and HELLS overexpression abolished the role of miR-335-5p restoration. Importantly, circAPLP2 could positively regulate HELLS expression by mediating miR-335-5p. Conclusion circAPLP2 triggered CRC malignant development by increasing HELLS expression via targeting miR-335-5p, which might be a novel strategy to understand and treat CRC.

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