The RNA-Binding Protein SMN as a Novel Player in Laryngeal Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) arises from the mucosal epithelium in the oral cavity, pharynx, sino-nasal region, and larynx. Laryngeal squamous cell carcinoma (LSCC) represents one-third of all head and neck cancers. Dysregulated RNA-related pathways define an important molecular signature in this aggressive carcinoma. The Survival Motor Neuron (SMN) protein regulates fundamental aspects of the RNA metabolism but, curiously, its role in cancer is virtually unknown. For the first time, here, we focus on the SMN in the cancer context. We conducted a pilot study in a total of 20 patients with LSCC where the SMN was found overexpressed at both the protein and transcript levels. By a cellular model of human laryngeal carcinoma, we demonstrated that the SMN impacts cancer-relevant behaviors and perturbs key players of cell migration, invasion, and adhesion. Furthermore, in LSCC we showed a physical interaction between the SMN and the epidermal growth factor receptor (EGFR), whose overexpression is an important feature in these tumors. This study proposes the SMN protein as a novel therapeutic target in LSSC and likely in the whole spectrum of HNSCC. Overall, we provide the first analysis of the SMN in human cancer.

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes

“…These genes were MKI67, SAMD5, OR51E, CD44, ERP44 and POLK. A recent report showed substantial upregulation SMN1 transcripts and SMN protein in LSCC 34 . It remains to be seen if an increase in SMN1 transcripts in LSCC is also accompanied with the elevated expression of C2A-2B-3-4.…”

“…In contrast, overexpression of SMN has been found to trigger neuroin ammation and the innate immune response in mice 33 . Recently, overexpression of SMN is recorded in patients with laryngeal squamous cell carcinoma (LSCC) 34 . Hence, a tight regulation of SMN appears to be critical for the proper function of the cellular metabolism.…”

Transcriptome- and proteome-wide effects of a circular RNA encompassing four early exons of the spinal muscular atrophy genes

“…These genes were MKI67 , SAMD5 , OR51E , CD44 , ERP44 and POLK . A recent report showed substantial upregulation of SMN1 transcripts and SMN protein in LSCC 34 . It remains to be seen if an increase in SMN1 transcripts in LSCC is also accompanied with the elevated expression of C2A–2B–3–4.…”

“…In contrast, overexpression of SMN has been found to trigger neuroinflammation and the innate immune response in mice 33 . Recently, overexpression of SMN was recorded in patients with laryngeal squamous cell carcinoma (LSCC) 34 . Hence, a tight regulation of SMN appears to be critical for the proper function of the cellular metabolism.…”

A comprehensive bioinformatics analysis of THOC3 highlights its potential role in pan-cancer and clinical significance in lung adenocarcinoma

“…Aberrant expression of the THO complex may lead to imbalance in intracellular information transmission, affecting normal cell growth and death processes. Recent research has progressively uncovered THOC3's role in cancer development , McCormack NM and colleagues demonstrated that silencing the THOC3 gene markedly increases SMN protein levels, which regulate RNA metabolism and are closely linked to cell migration, invasion, and adhesion [22,23] . Yu T and colleagues discovered that elevated THOC3 expression leads to an increase in PFKFB4 levels, which consequently enhances glycolysis and facilitates the progression and motility of LUSC cells [24] .…”