Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer

Dharavath, Bhasker; Butle, Ashwin; Pal, Ankita; Desai, Sanket; Upadhyay, Pawan; Rane, Aishwarya; Khandelwal, Risha; Manavalan, Sujith; Thorat, Rahul; Sonawane, Kavita; Vaish, Richa; Gera, Poonam; Bal, Munita; D’Cruz, Anil; Nair, Sudhir; Dutt, Amit

doi:10.1038/s42003-023-04437-6

Cited by 6 publications

(6 citation statements)

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“…Porphyromonas gingivalis is also reported to increase the invasiveness of the oral cancer cells, via induction and activation of pro‐MMP9 48 . Similar correlation is also observed in abundance of Fusobacterium and expression of MMP10 in tongue cancer, 40 a biomarker of lymph node metastases mechanistically shown to be driving invasion and migration in tongue cancer 49 . Details of the mechanistic involvement of the 2 gram‐negative opportunistic pathogens with oral cancer has been reviewed elsewhere 50,51 .…”

Section: Microbes Associated With Head and Neck Squamous Cell Carcinomamentioning

confidence: 84%

“… 48 Similar correlation is also observed in abundance of Fusobacterium and expression of MMP10 in tongue cancer, 40 a biomarker of lymph node metastases mechanistically shown to be driving invasion and migration in tongue cancer. 49 Details of the mechanistic involvement of the 2 gram‐negative opportunistic pathogens with oral cancer has been reviewed elsewhere. 50 , 51 As bacteria remain the dominant species of the metagenome, the association analysis warrants a careful inspection and requires supporting biological assessment of the role of cancer associated pathogens in the cancer microenvironment.…”

Section: Microbes Associated With Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

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Influence of pathogens on host genome and epigenome in development of head and neck cancer

Desai

2023

Cancer Reports

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BackgroundHead and neck cancer (HNSCC) is a heterogeneous group of cancers, affecting multiple regions such as oral cavity, pharynx, larynx, and nasal region, each showing a distinct molecular profile. HNSCC accounts for more than 6 million cases worldwide, soaring mainly in the developing countries.Recent findingsThe aetiology of HNSCC is complex and multifactorial, involving both genetic and environmental factors. The critical role of microbiome, which includes bacteria, viruses, and fungi, is under spotlight due to the recent reports on their contribution in the development and progression of HNSCC. This review focuses on the effect of opportunistic pathogens on the host genome and epigenome, which contributes to the disease progression. Drawing parallels from the host‐pathogen interactions observed in other tumour types arising from the epithelial tissue such as colorectal cancer, the review also calls attention to the potential explorations of the role of pathogens in HNSCC biology and discusses the clinical implications of microbiome research in detection and treatment of HNSCC.ConclusionOur understanding of the genomic effects of the microbes on the disease progression and the mechanistic insights of the host‐pathogen interaction will pave way to novel treatment and preventive approaches in HNSCC.

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Section: Microbes Associated With Head and Neck Squamous Cell Carcinomamentioning

confidence: 84%

Section: Microbes Associated With Head and Neck Squamous Cell Carcinomamentioning

confidence: 99%

Influence of pathogens on host genome and epigenome in development of head and neck cancer

Desai

2023

Cancer Reports

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“…AW13516 52 , AW8507 52 , NT-8e 53 , and OT9 53 , 54 head and neck cancer (HNSCC) cell lines 55 , 56 were obtained from Tata Memorial Hospital (Mumbai), while the NIH/3T3 (CRL-1658) cell line was procured from the American Type Culture Collection (ATCC). The cell lines were authenticated by DNA short tandem repeat (STR) profiling using the Promega Geneprint 10 system in conjugation with the GeneMarker HID software tool.…”

Section: Methodsmentioning

confidence: 99%

Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications

Dharavath,

Butle,

Chaudhary

et al. 2024

npj Precis. Onc.

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Head and neck cancer is a major cause of morbidity and mortality worldwide. The identification of genetic alterations in head and neck cancer may improve diagnosis and treatment outcomes. In this study, we report the identification and functional characterization of UBE3C-LRP5 translocation in head and neck cancer. Our whole transcriptome sequencing and RT-PCR analysis of 151 head and neck cancer tumor samples identified the LRP5-UBE3C and UBE3C-LRP5 fusion transcripts in 5.3% of patients of Indian origin (n = 151), and UBE3C-LRP5 fusion transcripts in 1.2% of TCGA-HNSC patients (n = 502). Further, whole genome sequencing identified the breakpoint of UBE3C-LRP5 translocation. We demonstrate that UBE3C-LRP5 fusion is activating in vitro and in vivo, and promotes the proliferation, migration, and invasion of head and neck cancer cells. In contrast, depletion of UBE3C-LRP5 fusion suppresses the clonogenic, migratory, and invasive potential of the cells. The UBE3C-LRP5 fusion activates the Wnt/β-catenin signaling by promoting nuclear accumulation of β-catenin, leading to upregulation of Wnt/β-catenin target genes, MYC, CCND1, TCF4, and LEF1. Consistently, treatment with the FDA-approved drug, pyrvinium pamoate, significantly reduced the transforming ability of cells expressing the fusion protein and improved survival in mice bearing tumors of fusion-overexpressing cells. Interestingly, fusion-expressing cells upon knockdown of CTNNB1, or LEF1 show reduced proliferation, clonogenic abilities, and reduced sensitivity to pyrvinium pamoate. Overall, our study suggests that the UBE3C-LRP5 fusion is a promising therapeutic target for head and neck cancer and that pyrvinium pamoate may be a potential drug candidate for treating head and neck cancer harboring this translocation.

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“…Recently, Dharavath et al [ 68 ] reported that miR-944 showed potential anti-metastatic activity in vivo and in vitro. They observed that miR-944 inhibited migration, invasion, and EMT of TSCC cells by targeting MMP-10.…”

Section: Mirnas As Either Tumor Suppressors or Oncomirs In Cancermentioning

confidence: 99%

“…They observed that miR-944 inhibited migration, invasion, and EMT of TSCC cells by targeting MMP-10. Hence they suggested that this miRNA could be a therapeutic target in TSCC patients [ 68 ].…”

Section: Mirnas As Either Tumor Suppressors or Oncomirs In Cancermentioning

confidence: 99%

MiRNA-related metastasis in oral cancer: moving and shaking

Eslami,

Khazeni,

Khanaghah

et al. 2023

Cancer Cell Int

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Across the world, oral cancer is a prevalent tumor. Over the years, both its mortality and incidence have grown. Oral cancer metastasis is a complex process involving cell invasion, migration, proliferation, and egress from cancer tissue either by lymphatic vessels or blood vessels. MicroRNAs (miRNAs) are essential short non-coding RNAs, which can act either as tumor suppressors or as oncogenes to control cancer development. Cancer metastasis is a multi-step process, in which miRNAs can inhibit or stimulate metastasis at all stages, including epithelial-mesenchymal transition, migration, invasion, and colonization, by targeting critical genes in these pathways. On the other hand, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two different types of non-coding RNAs, can regulate cancer metastasis by affecting gene expression through cross-talk with miRNAs. We reviewed the scientific literature (Google Scholar, Scopus, and PubMed) for the period 2000–2023 to find reports concerning miRNAs and lncRNA/circRNA-miRNA-mRNA networks, which control the spread of oral cancer cells by affecting invasion, migration, and metastasis. According to these reports, miRNAs are involved in the regulation of metastasis pathways either by directly or indirectly targeting genes associated with metastasis. Moreover, circRNAs and lncRNAs can induce or suppress oral cancer metastasis by acting as competing endogenous RNAs to inhibit the effect of miRNA suppression on specific mRNAs. Overall, non-coding RNAs (especially miRNAs) could help to create innovative therapeutic methods for the control of oral cancer metastases.

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Role of miR-944/MMP10/AXL- axis in lymph node metastasis in tongue cancer

Cited by 6 publications

References 50 publications

Influence of pathogens on host genome and epigenome in development of head and neck cancer

Influence of pathogens on host genome and epigenome in development of head and neck cancer

Recurrent UBE3C-LRP5 translocations in head and neck cancer with therapeutic implications

MiRNA-related metastasis in oral cancer: moving and shaking

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