Nestin protein affects the maintenance of stem characteristics of colorectal cancer cells based on p53 dependent pathway.

Abstract

Colorectal cancer (CRC) is a tumor with high incidence and poor prognosis. An increasing number of studies have shown that intermediate filament proteins, such as nestin, participate in the regulation of tumor progression. However, the mechanism related to CRC is complex, and the role and underlying mechanism of nestin have not been elucidated in CRC. We conducted quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blot analyses to examine the mRNA and protein levels in CRC and normal tissues. siRNAs targeting Nestin were transfected into CRC cells and then cell counting kit-8 (CCK-8), 5-ethynyl-2-deoxyuridine (EdU), sphere formation, and transwell analyses were used to assess the role of nestin in the proliferation, stem activity, migration, and invasive ability of CRC cells. Afterwards, nestin was overexpressed in CRC cells and P53 was overexpressed as a rescue group. CCK-8, EdU dyeing, sphere formation, and transwell assay was used to evaluated the role of Nestin/p53 axis in CRC cells. We found high nestin expression and low p53 expression in CRC tissues and cells. Functionally, silencing of nestin suppressed the multiplication, stemness, and metastatic ability of Caco-2 and RKO cells. Encouragingly, rescue experiments suggested that overexpression of p53 partly restored the impacts of nestin overexpression on the viability, proliferation, and metastatic ability of CRC cells. We confirmed that nestin and p53 play a functional role in the progression of CRC, and they may act as potential therapeutic targets for CRC treatment.