Molecular networks of FOXP family: dual biologic functions, interplay with other molecules and clinical implications in cancer progression

AbstractThough Forkhead box P (FOXP) transcription factors comprising of FOXP1, FOXP2, FOXP3 and FOXP4 are involved in the embryonic development, immune disorders and cancer progression, the underlying function of FOXP3 targeting CD4 + CD25+ regulatory T (Treg) cells and the dual roles of FOXP proteins as an oncogene or a tumor suppressor are unclear and controversial in cancers to date. Thus, the present review highlighted research history, dual roles of FOXP proteins as a tumor suppressor or an oncogene, their molecular networks with other proteins and noncoding RNAs, cellular immunotherapy targeting FOXP3, and clinical implications in cancer progression.

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HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

International Journal of Molecular Sciences ◽

10.3390/ijms23010009 ◽

2021 ◽

Vol 23 (1) ◽

pp. 9

Author(s):

Seho Jeong ◽

Soo-A Kim ◽

Sang-Gun Ahn

Keyword(s):

Cell Migration ◽

Tumor Suppressor ◽

Cancer Progression ◽

Regulatory Networks ◽

Suppressor Gene ◽

Malignant Progression ◽

Luciferase Assay ◽

Regulatory Interactions ◽

Forkhead Box ◽

Microarray Profiling

Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3′-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.

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LINC00261: a burgeoning long noncoding RNA related to cancer

Cancer Cell International ◽

10.1186/s12935-021-01988-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Menggang Zhang ◽

Fang Gao ◽

Xiao Yu ◽

Qiyao Zhang ◽

Zongzong Sun ◽

...

Keyword(s):

Tumor Suppressor ◽

Cancer Progression ◽

Noncoding Rna ◽

Cancer Colorectal ◽

Tumor Development ◽

Noncoding Rnas ◽

Biological Processes ◽

Biological Mechanisms ◽

Protein Coding ◽

Cellular Processes

AbstractLong noncoding RNAs (lncRNAs), are transcripts longer than 200 nucleotides that are considered to be vital regulators of many cellular processes, particularly in tumorigenesis and cancer progression. long intergenic non-protein coding RNA 261 (LINC00261), a recently discovered lncRNA, is abnormally expressed in a variety of human malignancies, including pancreatic cancer, gastric cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, breast cancer, laryngeal carcinoma, endometrial carcinoma, esophageal cancer, prostate cancer, choriocarcinoma, and cholangiocarcinoma. LINC00261 mainly functions as a tumor suppressor that regulates a variety of biological processes in the above-mentioned cancers, such as cell proliferation, apoptosis, motility, chemoresistance, and tumorigenesis. In addition, the up-regulation of LINC00261 is closely correlated with both favorable prognoses and many clinical characteristics. In the present review, we summarize recent research documenting the expression and biological mechanisms of LINC00261 in tumor development. These findings suggest that LINC00261, as a tumor suppressor, has bright prospects both as a biomarker and a therapeutic target.

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Computational study for suppression of CD25/IL-2 interaction

Biological Chemistry ◽

10.1515/hsz-2020-0326 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Moein Dehbashi ◽

Zohreh Hojati ◽

Majid Motovali-bashi ◽

Mazdak Ganjalikhani-Hakemi ◽

Akihiro Shimosaka ◽

...

Keyword(s):

Small Molecules ◽

Cancer Progression ◽

Immune Escape ◽

De Novo ◽

Computational Study ◽

Treg Cells ◽

Homology Search ◽

Small Interfering Rnas

AbstractCancer recurrence presents a huge challenge in cancer patient management. Immune escape is a key mechanism of cancer progression and metastatic dissemination. CD25 is expressed in regulatory T (Treg) cells including tumor-infiltrating Treg cells (TI-Tregs). These cells specially activate and reinforce immune escape mechanism of cancers. The suppression of CD25/IL-2 interaction would be useful against Treg cells activation and ultimately immune escape of cancer. Here, software, web servers and databases were used, at which in silico designed small interfering RNAs (siRNAs), de novo designed peptides and virtual screened small molecules against CD25 were introduced for the prospect of eliminating cancer immune escape and obtaining successful treatment. We obtained siRNAs with low off-target effects. Further, small molecules based on the binding homology search in ligand and receptor similarity were introduced. Finally, the critical amino acids on CD25 were targeted by a de novo designed peptide with disulfide bond. Hence we introduced computational-based antagonists to lay a foundation for further in vitro and in vivo studies.

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Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms22073571 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3571

Author(s):

Bonglee Kim ◽

Ji-Eon Park ◽

Eunji Im ◽

Yongmin Cho ◽

Jinjoo Lee ◽

...

Keyword(s):

Cancer Progression ◽

Animal Studies ◽

Molecular Mechanisms ◽

Future Research ◽

Clinical Implications ◽

Research Perspectives ◽

Current Review ◽

Gold Silver ◽

Significant Efficacy ◽

Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

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