Evaluation of the simultaneous effects of KRAS G12V and LCS6 alterations on the behavior of head and neck squamous cell carcinoma.

Abstract

Background: Head and neck squamous cell carcinomas are the seventh most common cancer accounting for 90 % of malignant neoplasia of the upper respiratory system. KRAS is a very important oncogene, leading to the suppression of apoptosis, and promoting the pathogenesis and development of tumors. MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules aberrantly expressed in various pathologies including regulation of tumor and metastasis-associated genes. Variant (rs61764370) of the let-7 miRNA complementary site of KRAS 3'-untranslated region (KRAS-LCS6) has been shown to disrupt the ability of miRNAs to target genes resulting in differential target mRNA and protein expression.

Methods: In this study, the effects of variant complementary site LCS6 of the let-7 miRNA in head and neck cancer were investigated in vitro using laryngeal carcinoma HEp-2 carrying G12V and LCS6 alterations in the KRAS gene. Non-cancer HEK-293 cells were also used as control cells.

Results: G12V mutation in the KRAS gene increases invasion capacity and is specifically active on the ERK pathway associated with metastasis. Alteration in the LCS6 region of the KRAS gene did not show additional effects compared to cells only carrying G12V mutation. Our results also showed that the coexistence of G12V and LCS6 alterations is lethal to specific cell types, UM-SCC-17A laryngeal cancer cells in our case.

Conclusions: The LCS6 region alteration of the KRAS may play a key role in further cancer progression, and more research is needed to fully understand the mechanisms by which the LCS6 alterations promote cancer progression.