Distinctive pattern of let-7 family microRNAs in aggressive carcinoma of the oral tongue in young patients

Abstract

Oral cavity squamous cell carcinoma may be more aggressive at presentation and recurrence in young patients compared with older patients. Dysregulation of microRNAs (miRNAs or miRs) has been associated with the development and prognosis of oral cavity cancer. The present study investigated miRNA expression in carcinoma of the oral tongue in young patients. miRNA expression profiles were evaluated in formalin-fixed, paraffin-embedded samples of tumor and normal mucosa from 12 patients aged <30 years old with squamous cell carcinoma of the tongue. The levels of let-7f-5p, miR-30b-5p and let-7e-5p were upregulated in tumors (P<0.05). The expression of let-7f-5p was upregulated in non-aggressive tumors, while the expression of let-7e-5p was upregulated in aggressive tumors, compared with the corresponding normal tissue. Aggressive tumors had higher levels of let-7c, miR-130a-3p, miR-361-5p, miR-99a-5p, miR-29c-3p and let-7d-5p than non-aggressive tumors (P<0.05). The findings remained significant for let-7c upon false-discovery rate correction. An excellent correlation was noticed on validation of NanoString counts by quantitative polymerase chain reaction. The comparison with published findings in adults demonstrated a unique miRNA signature in young patients with aggressive disease. Aggressive oral cavity cancer in patients <30 years old is associated with a distinctive expression pattern of the let-7 family. Larger studies including direct comparison with older patients are warranted.

Molecular basis of oral squamous cell carcinoma in young patients: Is it any different from older patients?

“…MicroRNAs (miRNAs) are small non‐coding RNA molecules that induce post‐transcriptional gene silencing. Hilly et al revealed an up‐regulation of let‐7 family miRNAs, let‐7f‐5p, miR‐30b‐5p, and let‐7e‐5p in TSCC of young patients (≤30 years) compared to normal tissue. Additionally, up‐regulation of let‐7c, miR‐130a‐3p, miR‐361‐5p, miR‐99a‐5p, miR‐29c‐3p was found, and let‐7d‐5p was associated with more aggressive tumors.…”

“…The variability observed in the incidence of OSCC in young patients is partly explained by the arbitrary use of different cut‐off values to determine age groups, making difficult comparison of results obtained by different authors. Although most studies use ages ranging from 30 to 50 years, the majority considers young patients as those aged below 40 . In this group of patients, the oral tongue is the most affected site (41.1%‐61.3%) and there still is a male predilection, with a male:female ratio of 1.6:1 to 2.6:1 .…”

“…Although most studies use ages ranging from 30 to 50 years, the majority considers young patients as those aged below 40. [6][7][8] In this group of patients, the oral tongue is the most affected site (41.1%-61.3%) and there still is a male predilection, with a male:female ratio of 1.6:1 to 2.6:1. 5,9,10 However, a higher proportion of never smokers and never drinkers young women have been described in some studies.…”

Let‐7c restores radiosensitivity and chemosensitivity and impairs stemness in oral cancer cells through inhibiting interleukin‐8

“…Let‐7a overexpression significantly inhibited the stemness signature and the chemoresistant abilities of HNSCC‐ALDH1 + cells . Moreover, one of the recent studies has indicated that there were higher levels of let‐7c and let‐7d‐5p in aggressive tongue tumors …”

“…15 Moreover, one of the recent studies has indicated that there were higher levels of let-7c and let-7d-5p in aggressive tongue tumors. 16 Accordingly, we sought to investigate the significance of let-7c in cancer stemness as other let-7 members play key roles in oral malignancy. First, we examined the expression of let-7c in normal, tumor, and metastasis tissues and showed the survival rate of patients in accordance with high or low expression of let-7c.…”