Investigation of the association between miR-181b, Bcl-2 and LRIG1 in oral verrucous carcinoma

Abstract

Abnormal expression of microRNAs (miRNAs) is involved in the development of and anti-apoptotic effects in various types of human cancer. However, miRNA-mediated regulation of oral verrucous carcinoma (OVC) remains to be elucidated. The present study aimed to investigate the expression of miR-181b in OVC and oral squamous cell carcinoma (OSCC). The expression levels of miR-181b were determined using reverse transcription-quantitative polymerase chain reaction. The expression levels of B-cell lymphoma 2 (Bcl-2) and leucine rich repeats and immunoglobulin like domains 1 (LRIG1), were evaluated using immunohistochemical staining. The correlation between Bcl-2 and LRIG1 expression was determined using a Pearson correlation analysis. The expression levels of miR-181b and Bcl-2 in OVC were significantly higher compared with normal mucosal tissue (NM); however, lower compared with the OSCC. The key target of miR-181b was LRIG1 and it was significantly lower in OVC tissues compared with NM tissue; however this was higher when compared with OSCC tissue. The expression levels of Bcl-2 were correlated with expression levels of LRIG1 in OVC tissues. Therefore, LRIG1 may be associated with anti-apoptotic function in OVC tissues.

Exploring the Role of EZH2 and BCL2 in Demarcating Oral Verrucous Hyperplasia and Verrucous Carcinoma

“…Deng et al and Jairajpuri et al also observed similar expression pattern in group II and III; however, Thennevan et al suggested very limited expression in verrucous lesions. 12 17 Corresponding with the previous studies we concur that a proportional rise in the BCL2 expression from group I to III reflects its part in disease progression by increasing the survival rate of neoplastic cells and allowing clones of the neoplastic cells to proliferate and differentiate. In group IV, BCL2 immunoexpression was exaggerated and primarily confined to peripheral cells of the tumor islands similar to studies conducted by Juneja et al and Sudha and Hemavathy ( Fig.…”

“…Several authors have illustrated overlapping pathways of EZH2 and BCL2 in certain lymphoid malignancies which have significant treatment implications. 17,18 In cholangiocarcinoma cells EZH2 inactivates p16 and p27 which further suppresses apoptosis. 29 However, no such pathways have been explored in oral lesions.…”

“…B cell lymphoma 2 (BCL2) localizes itself in the outer membrane of mitochondria, where it promotes cell survival and inhibits apoptosis by blocking cytochrome C followed by inactivation of the caspases. 17 22 23 Although few studies have explored BCL2 expression in OVH and OVC, only a single study was conducted using EZH2 in the same lesions. 16 In the present study, we have analyzed the immunohistochemical expression of EZH2 and BCL2 concomitantly with an attempt to distinguish OVH and OVC.…”

Análise da expressão de miRNAs em lesões potencialmente malignas e no câncer de lábio

“…Tendo em vista as limitações observadas para classificação das displasias epiteliais, assim como, da displasia epitelial severa e o carcinoma espinocelular de lábio inferior, buscamos verificar neste trabalho a expressão dos miRNA-181b, miRNA-21, miRNA-31 e miRNA-345 nas queilites actínicas e nos carcinomas espinocelulares de lábio inferior. A seleção destes miRNAs foi realizada com base em estudos prévios de leucoplasia bucal, outra lesão potencialmente maligna, (CERVIGNE et al, 2009;YANG et al, 2011;XIAO et al, 2012;BRITO et al, 2014;MAIMAITI et al, 2015;ZHU et al, 2015;HUNG et al, 2016) foi verificado nas neoplasias malignas mais avançadas (CERVIGNE et al, 2009;YANG et al, 2011;YANG et al, 2013;BRITO et al, 2014;DENG et al, 2016 Nossos resultados da expressão do miRNA-21 confirmam estudos prévios, em carcinomas hepatocelulares (MENG et al, 2007) e em carcinomas espinocelulares de cabeça e pescoço (LI et al, 2009;LIU, X. et al, 2009;CHEN et al, 2013;HEDBACK et al, 2014;SUN et al, 2014), que descreveram uma associação entre a maior expressão de miRNA-21 com a progressão destas neoplasias malignas. Este aumento da expressão do miRNA-21 como descrito no presente estudo, foi igualmente reportado nas leucoplasias bucais (CERVIGNE et al, 2009, BRITO et al, 2014ZHU et al, 2014;HUNG et al, 2015) e nos carcinomas espinocelulares de boca (LI et al, 2009;SIOW et al, 2014;ZHOU et al, 2014;TROIANO et al, 2018) A análise do miRNA-345 em lesões potencialmente malignas de boca como as leucoplasias bucais, foram realizados em poucos estudos (CERVIGNE et al, 2009;BRITO et al, 2014), sendo descrito um aumento da expressão deste miRNA nestas lesões, o que contrasta com nossos resultados.…”

“…Outro miRNA que vem sendo investigado nos processos neoplásicos, incluindo os carcinomas espinocelulares de boca, é o miRNA-31 (LIU, C. J. et al, 2010;LIU, C. J. et al, 2012;SIOW et al, 2014;YAN et al, 2017 Outro miRNA que apresentou particular interesse em estudos iniciais do desenvolvimento tumoral em boca é o miRNA-181b, membro da família de miRNA-181s (CERVIGNE et al, 2009;YANG, C. C. et al, 2011;DENG et al, 2016). A família do miRNA-p27Kipl e Bcl-2, sendo a regulação do miRNA-181 mediada pelo silenciamento de fatores de transcrição específicos nos diferentes tipos de cânceres (YANG, C. C. et al, 2011;BRITO, J.…”