Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer

Muthuramalingam, Pandiyan; Akassh, Sakthivel; Rithiga, Saravanan Bhavanisha; Prithika, Senthilkumar; Gunasekaran, Ravikumar; Shin, Hyunsuk; Kumar, Randhir; Venkidasamy, Baskar; Kim, Jin-Wook

doi:10.1016/j.ejphar.2022.175479

Cited by 15 publications

(10 citation statements)

References 45 publications

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“…Moreover, based on the previous literature, 26 , 27 we selected important cancer-related genes, cell-cycle regulatory genes, and cytokine genes and analyzed their interconnections using in silico network analyses: STRING, GeneMANIA, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. 28 , 29 The network analyses indicated that most of the selected genes are highly interlinked and involved in regulating apoptosis, lymphocyte differentiation, cytokine-mediated signaling pathways, and stress responses. Moreover, the analyses also identified genes connected with RCAS1 ( Figures 5 A–5C).…”

Section: Resultsmentioning

confidence: 99%

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Sivasankar,

Hewawaduge,

Muthuramalingam

et al. 2023

Molecular Therapy - Nucleic Acids

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Section: Resultsmentioning

confidence: 99%

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Sivasankar,

Hewawaduge,

Muthuramalingam

et al. 2023

Molecular Therapy - Nucleic Acids

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“…The results of the survival analysis highlight the significant gene expression of a few prognostic genes. These prognostic genes are also known as unfavorable genes because their expression may reduce the overall survival of CAC patients [ 26 , 82 ]. Phytocompounds, or drugs mainly targeting these prognostic genes, might be useful for cachexia therapy.…”

Section: Discussionmentioning

confidence: 99%

“…For this purpose, the ExpressAnalyst tool ( accessed on 4 September 2023) was used to check the involvement of the obtained genes in many CAC-related pathways. Further, the selected unique genes were imported into the Network Analyst 3.0. database ( accessed on 7 September 2023) for imputing the adipose tissue-specific CAC-related pathway analysis by the inbuilt KEGG [ 26 , 102 ].…”

Section: Methodsmentioning

confidence: 99%

“…Application of this modern-era approach to traditional/conventional medicines is an evolving approach for the identification of bioactive compounds and their putative molecular targets. This method includes the following steps: (i) Data mining; (ii) construction of networks and analysis; and (iii) validation of results (in silico, in vitro, and in vivo) [ 25 , 26 ]. In recent years, this method has been used for the identification of target bioactive compounds from plants against several life-threatening diseases, such as COVID-19 [ 10 , 27 ], lung cancer [ 26 , 28 ], cervical cancer [ 29 ], oral cancer [ 30 ], and neurological diseases [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…This method includes the following steps: (i) Data mining; (ii) construction of networks and analysis; and (iii) validation of results (in silico, in vitro, and in vivo) [ 25 , 26 ]. In recent years, this method has been used for the identification of target bioactive compounds from plants against several life-threatening diseases, such as COVID-19 [ 10 , 27 ], lung cancer [ 26 , 28 ], cervical cancer [ 29 ], oral cancer [ 30 ], and neurological diseases [ 31 , 32 ]. Even though this promising network pharmacology approach explores traditional herbal medicines against several cancer types and neurological diseases, the application of this method to identify specific targets against muscle-wasting cachexia remains less understood.…”

Section: Introductionmentioning

confidence: 99%

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Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach

Muthamil,

Muthuramalingam,

Kim

et al. 2023

IJMS

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Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

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Phosphoinositide 3‐Kinase Inhibitors from Gladiolus Segetum Ker‐Gawl Corms Supported by Network Pharmacology

Khalaf Mahmoud,

Abdelwahab,

Alzahraa Mokhtar

et al. 2024

Chemistry & Biodiversity

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Gladiolus segetum Ker‐Gawl corms total extract exhibited remarkable in vitro anti‐proliferative effects against panel of cancer cell lines; including human colon carcinoma (Caco‐2), human breast cancer (MCF7) and hepatocellular carcinoma (HepG2) cell lines with IC50 values of 7.4, 9.1 and 11.2 µg/ml, respectively. The total ethanolic extract of G. segetum Ker‐Gawl corms was subjected to untargeted metabolomics profiling using LC‐HR‐ESI‐MS, which revealed the presence of various clusters of phytoconstituents as triterpenes, anthraquinones, flavonoids and phenolic derivatives. Network pharmacology study was performed for all identified compounds, the formed networks identified 73 intersected genes. The diagrammatic illustration of the top pathways revealed that phosphoinositide 3‐kinase (PI3K) gene is the effective dominant gene in the top four KEGG pathways. Upon molecular docking and molecular dynamics investigation, kaempferol‐3‐O‐glucopyranoside was suggested to be key anticancer metabolite. Interestingly, cytotoxic investigation of this compound revealed potential activity against the tested cancer cell lines (Caco‐2, MCF7 and HepG2) with IC50 values of 6.2, 8.5 and 9.3 µg/ml, respectively. The present study highlighted the potential of G. segetum Ker‐Gawl as a promising source of interesting anticancer scaffolds.

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Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer

Cited by 15 publications

References 45 publications

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach

Phosphoinositide 3‐Kinase Inhibitors from Gladiolus Segetum Ker‐Gawl Corms Supported by Network Pharmacology

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