Exploring Dysregulated Signaling Pathways in Cancer

Nisar, Sabah; Hashem, Sheema; Macha, Muzafar A.; Yadav, Santosh Kumar; Muralitharan, Sankavi; Therachiyil, Lubna; Sageena, Geetanjali; Al‐Naemi, Hamda; Haris, Mohammad; Bhat, Ajaz A.

doi:10.2174/1381612826666200115095937

Cited by 25 publications

(18 citation statements)

References 300 publications

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“…It was found that TE inhibited the viability of U87 cells more profoundly as compared to the normal astrocytes. This selective inhibition of U87 cells by TE could be attributed to the fact that several signalling pathways show dysregulation in cancer cells [19], and TE extract might modulate any of these pathways. However, more studies are needed to infer the exact mechanism for the selective inhibition of the U87 cells.…”

Section: Discussionmentioning

confidence: 99%

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells

Baba¹,

Vahedi

Ahmad

et al. 2022

BioMed Research International

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Crocus sativus (C. sativus) is considered as the costliest spice and an important medicinal plant. Herein, we investigated the effects of tepal extract (TE) of C. sativus on the viability of the human glioblastoma cells. Results revealed that TE significantly ( P < 0.05 ) inhibited the proliferation of U87 glioblastoma cells in a dose-dependent manner with comparatively lower toxic effects against normal astrocytes. The I C 50 of TE against U87 glioblastoma cells was found to be 130 μg/mL as compared to 600 μg/mL against normal astrocytes. TE also inhibited the colony formation of U87 cells significantly ( P < 0.05 ). The AO/EB and Annexin V/PI staining assays indicated that TE stimulated apoptosis in U87 cells dose dependently. The early and late apoptotic U87 cells increased from 0.66% and 2.3% at control to 14.2% and 21.4% at 260 μg/mL of TE. Moreover, TE caused upregulation of Bax and suppression of Bcl-2. Wound healing assay showed that migration of the U87 cells was suppressed significantly ( P < 0.05 ) at 80 μg/mL of TE. Taken together, these results suggest that TE exhibits antiproliferative effects against U87 glioma cells and may prove to be an important source of natural anticancer agents.

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Section: Discussionmentioning

confidence: 99%

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells

Baba¹,

Vahedi

Ahmad

et al. 2022

BioMed Research International

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“…9e). The defects of these pathways are reflected in the pathogenesis of various types of tumors including bladder cancer [38]- [40].…”

Section: E the Prognostic Signatures Of Mrmsmentioning

confidence: 99%

Identification of MicroRNA Regulatory Modules by Clustering MicroRNA-Target Interactions

Yang

Wan

2020

IEEE Access

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Identification of microRNA regulatory modules can help decipher microRNA synergistic regulatory mechanism in the development and progression of complex diseases, especially cancers. Experimentally validated microRNA-target interactions provide strong direct evidence for the analysis of microRNA regulatory functions. We here developed a novel computational framework named CMIN to identify microRNA regulatory modules by performing link clustering on such experimentally verified microRNA-target interactions. CMIN runs in two main steps: it first utilizes convolutional autoencoders to extract high-level microRNA-target interaction features from the expression profile data, and then applied affinity propagation clustering algorithm to interaction feature to obtain overlapping microRNA-target clusters. Clusters with significant synergy correlations are considered as microRNA regulatory modules. We tested the proposed framework and other three existing methods on three types of cancer data sets from TCGA (The Cancer Genome Atlas). The results showed that the microRNA regulatory modules detected by CMIN exhibit stronger topological correlation and more functional enrichment compared with other methods. Availability: The supplementary files of CMIN are available at https://github.com/snryou/CMIN.

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“…The disruption of pathway regulation by oncogenic mutations or the abnormal expression of key genes promotes tumor onset and progression. As for other kind of tumors, the identification of ES targetable molecular markers and their potential inhibitors will be useful for the development of tailored therapeutic regimens [ 22 ]. In this regard, an overexpression of VEGF (vascular endothelial growth factor), an important signaling protein involved in the angiogenesis pathway, has been reported in ES [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy

Russi

Sgambato

Bochicchio

et al. 2021

IJMS

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Epithelioid sarcoma (ES) is a rare disease representing <1% of soft tissue sarcomas. Current therapies are based on anthracycline alone or in combination with ifosfamide or other cytotoxic drugs. ES is still characterized by a poor prognosis with high rates of recurrence. Indeed, for years, ES survival rates have remained stagnant, suggesting that conventional treatments should be revised and improved. New therapeutic approaches are focused to target the key regulators of signaling pathways, the causative markers of tumor pathophysiology. To this end, we selected, among the drugs to which an ES cell line is highly sensitive, those that target signaling pathways known to be dysregulated in ES. In particular, we found a key role for GSK-3β, which results in up-regulation in tumor versus normal tissue samples and associated to poor prognosis in sarcoma patients. Following this evidence, we evaluated CHIR99021, a GSK-3 inhibitor, as a potential drug for use in ES therapy. Our data  highlight that, in ES cells, CHIR99021 induces cell cycle arrest, mitotic catastrophe (MC) and autophagic response, resulting in reduced cell proliferation. Our results support the potential efficacy of CHIR99021 in ES treatment and encourage further preclinical and clinical studies.

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Exploring Dysregulated Signaling Pathways in Cancer

Cited by 25 publications

References 300 publications

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells

Crocus sativus L. Tepal Extract Induces Apoptosis in Human U87 Glioblastoma Cells

Identification of MicroRNA Regulatory Modules by Clustering MicroRNA-Target Interactions

CHIR99021, trough GSK-3β Targeting, Reduces Epithelioid Sarcoma Cell Proliferation by Activating Mitotic Catastrophe and Autophagy

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