Disentangling the signaling pathways of mTOR complexes, mTORC1 and mTORC2, as a therapeutic target in glioblastoma

Background: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. Methods: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. Results: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, regulating miRNAs and proteins, and such shows its significant potential as a therapeutic cancer target. Conclusion: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

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Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.607764 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaobo Zhu ◽

Yau Tsz Chan ◽

Patrick S. H. Yung ◽

Rocky S. Tuan ◽

Yangzi Jiang

Keyword(s):

Extracellular Matrix ◽

Signaling Pathways ◽

Bone Remodeling ◽

Molecular Mechanism ◽

Subchondral Bone ◽

Therapeutic Target ◽

Therapeutic Targets ◽

Regenerative Therapies

There is emerging awareness that subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). This review presents recent investigations on the cellular and molecular mechanism of subchondral bone remodeling, and summarizes the current interventions and potential therapeutic targets related to OA subchondral bone remodeling. The first part of this review covers key cells and molecular mediators involved in subchondral bone remodeling (osteoclasts, osteoblasts, osteocytes, bone extracellular matrix, vascularization, nerve innervation, and related signaling pathways). The second part of this review describes candidate treatments for OA subchondral bone remodeling, including the use of bone-acting reagents and the application of regenerative therapies. Currently available clinical OA therapies and known responses in subchondral bone remodeling are summarized as a basis for the investigation of potential therapeutic mediators.

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A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

Scientific Reports ◽

10.1038/srep36132 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Aneesha Radhakrishnan ◽

Vishalakshi Nanjappa ◽

Remya Raja ◽

Gajanan Sathe ◽

Vinuth N. Puttamallesh ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Signaling Pathways ◽

Cell Lines ◽

Squamous Cell ◽

Therapeutic Target ◽

Neck Squamous Cell Carcinoma ◽

Dual Specificity ◽

Hnscc Cell

Abstract Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC.

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Progress in research on the role of Omi/HtrA2 in neurological diseases

Reviews in the Neurosciences ◽

10.1515/revneuro-2018-0004 ◽

2019 ◽

Vol 30 (3) ◽

pp. 279-287 ◽

Cited By ~ 2

Author(s):

Xiao Juan Su ◽

Lingyi Huang ◽

Yi Qu ◽

Dezhi Mu

Keyword(s):

Cell Death ◽

Signaling Pathways ◽

Serine Protease ◽

Brain Damage ◽

Therapeutic Target ◽

Neurological Diseases ◽

Mitochondrial Matrix ◽

Ischemic Brain ◽

External Signals

Abstract Omi/HtrA2 is a serine protease present in the mitochondrial space. When stimulated by external signals, HtrA2 is released into the mitochondrial matrix where it regulates cell death through its interaction with apoptotic and autophagic signaling pathways. Omi/HtrA2 is closely related to the pathogenesis of neurological diseases, such as neurodegeneration and hypoxic ischemic brain damage. Here, we summarize the biological characteristics of Omi/HtrA2 and its role in neurological diseases, which will provide new hints in developing Omi/HtrA2 as a therapeutic target for neurological diseases.

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Molecular Mechanisms of Glial Cells Related Signaling Pathways Involved in the Neuroinflammatory Response of Depression

Mediators of Inflammation ◽

10.1155/2020/3497920 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Junhui Wang ◽

Jie Qin ◽

Peng Wang ◽

Yu Sun ◽

Qi Zhang

Keyword(s):

Psychiatric Disorders ◽

Signaling Pathways ◽

Glial Cells ◽

Therapeutic Target ◽

Molecular Mechanisms ◽

Pathological Change ◽

Basic Knowledge ◽

Pathological Features ◽

Potential Therapeutic Target ◽

Neuroinflammatory Response

Dysfunction of the glial cells, such as astrocytes and microglia, is one of the pathological features in many psychiatric disorders, including depression, which emphasizes that glial cells driving neuroinflammation is not only an important pathological change in depression but also a potential therapeutic target. In this review, we summarized a recent update about several signaling pathways in which glial cells may play their roles in depression through neuroinflammatory reactions. We focused on the basic knowledge of these signaling pathways by elaborating each of them. This review may provide an updated image about the recent advances on these signaling pathways that are essential parts of neuroinflammation involved in depression.

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Circular RNA as a potential diagnostic and/or therapeutic target for endometriosis

Biomarkers in Medicine ◽

10.2217/bmm-2020-0167 ◽

2020 ◽

Vol 14 (13) ◽

pp. 1277-1287

Author(s):

Parisa M Dana ◽

Mona Taghavipour ◽

Hamed Mirzaei ◽

Bahman Yousefi ◽

Bahram Moazzami ◽

...

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Therapeutic Target ◽

Noncoding Rnas ◽

Circular Rna ◽

Circular Rnas ◽

Biological Functions ◽

Parental Gene

Endometriosis is a pathology form of endometrium that behaves in a similar way to malignancies, such as invasion and resistance to apoptosis. Circular RNAs (CircRNAs) are a class of noncoding RNAs that have several biological functions including, miRNA sponging, sequestering of proteins, enhancing parental gene expression and translation resulting in polypeptides. In this review, we highlighted the roles of circRNAs as potential diagnostic and therapeutic biomarkers in endometriosis. Moreover, we summarized the roles of circRNAs in the pathogenesis of endometriosis via different signaling pathways, such as the miRNA network and apoptosis.

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Dual inhibition of the mTORC1 and mTORC2 signaling pathways is a promising therapeutic target for adult T-cell leukemia

Cancer Science ◽

10.1111/cas.13431 ◽

2017 ◽

Vol 109 (1) ◽

pp. 103-111 ◽

Cited By ~ 14

Author(s):

Takahito Kawata ◽

Kohei Tada ◽

Masayuki Kobayashi ◽

Takashi Sakamoto ◽

Yoko Takiuchi ◽

...

Keyword(s):

T Cell ◽

Signaling Pathways ◽

Therapeutic Target ◽

T Cell Leukemia ◽

Cell Leukemia ◽

Adult T Cell Leukemia ◽

Promising Therapeutic Target ◽

Dual Inhibition

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Signaling pathways as therapeutic target in tumor treatment

Vedic Research International Cell Signaling ◽

10.14259/cs.v2i1.97 ◽

2014 ◽

Vol 2 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Mohamed Hassan ◽

Abderlouahid El-Khattouti ◽

Youssef Haikel ◽

Mosaad Megahed

Keyword(s):

Signaling Pathways ◽

Therapeutic Target ◽

Tumor Treatment

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Extracellular NM23 Protein as a Therapeutic Target for Hematologic Malignancies

Advances in Hematology ◽

10.1155/2012/879368 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 9

Author(s):

Junko Okabe-Kado ◽

Takashi Kasukabe ◽

Yasuhiko Kaneko

Keyword(s):

Signaling Pathways ◽

Therapeutic Target ◽

Elevated Serum ◽

Hematologic Malignancies ◽

Mapk Signaling ◽

Myelogenous Leukemia ◽

Poor Prognostic Factor ◽

Normal Peripheral Blood ◽

Growth And Survival

An elevated serum level of NM23-H1 protein is a poor prognostic factor in patients with various hematologic malignancies. The extracellular NM23-H1 protein promotes thein vitrogrowth and survival of acute myelogenous leukemia (AML) cells and inversely inhibits thein vitrosurvival of normal peripheral blood monocytes in primary culture at concentrations equivalent to the levels found in the serum of AML patients. The growth and survival promoting activity to AML cells is associated with cytokine production and activation of mitogen-activated protein kinases (MAPKs) and signal transducers and activators of transcription (STAT) signaling pathways. Inhibitors specific for MAPK signaling pathways inhibit the growth/survival-promoting activity of NM23-H1. These findings indicate a novel biological action of extracellular NM23-H1 and its association with poor prognosis. These results suggest an important role of extracellular NM23-H1 in the malignant progression of leukemia and a potential therapeutic target for these malignancies.

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