TPX2 knockdown mediates p53 activation to induce autophagy and apoptosis for anti-colorectal cancer effects.

Abstract

Colorectal cancer (CRC) exhibits high morbidity and mortality worldwide. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) impacts various cancers; however, mechanism of TPX2 in CRC remains unclear. Xenograft nude mouse models were constructed by subcutaneous injection of HCT116 cells with sh-NC, sh-TPX2, OE-NC, and OE-TPX2 transfection. Following the test of tumor growth, immunohistochemistry and TUNEL staining were done. In vitro, HCT116, RKO, and SW480 cells were divided into sh-NC, sh-TPX2, and sh-TPX2 + 3-methyladenine (3-MA, autophagy inhibitor) groups. Further, sh-p53 and rapamycin (RA, autophagy agonist) were added in HCT116 cells. EdU staining, flow cytometry, transparent electron microscopy, and Western blot were performed. Comparing with sh-NC group, sh-TPX2 inhibited tumor growth and Ki67 expression, and increased LC3-II expression and apoptosis, whereas OE-TPX2 group presented an opposite trend. In vitro, HCT116 and RKO cells in sh-TPX2 group enhanced apoptosis and LC3 II/LC3 I expression, and inhibited proliferation and P62 expression, which were reversed after further 3-MA intervention. The above results were not found in SW480 cells. Moreover, compared to sh-TPX2 group, sh-TPX2 + RA group enhanced apoptosis and autophagy, and suppressed the proliferation of HCT116 cells, which were reversed following further sh-p53 intervention. Therefore, sh-TPX2 mediated p53 activation to induce autophagy for anti-CRC effects, providing new ideas for CRC treatment.