Abstract
Photodynamic therapy (PDT) is considered a potential treatment regimen for colorectal cancer cases (CRC). p53 signaling and the miR-124/iASPP axis play an essential role in the PDT resistance of CRC cells. PDT treatment downregulated NEAT1 expression in p53wt HCT116 and RKO cells. In these two cell lines, NEAT1 silencing enhanced the suppressive effects of PDT on cell viability and apoptosis. Within the subcutaneously implanted tumor model, NEAT1 silencing enhanced PDT-induced suppression on tumor growth. Regarding p53-deleted HCT116 cells, PDT only moderately affected cell proliferation but induced downregulation of NEAT1. NEAT1 directly targeted miR-124, acting as a ceRNA, competing with iASPP for miR-124 binding, and counteracting miR-124–mediated repression on iASPP under PDT treatment. NEAT1 silencing was enhanced, whereas miR-124 inhibition attenuated PDT effects on CRC cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells. miR-124 negatively correlated with NEAT1 and iASPP, respectively, whereas NEAT1 and iASPP positively correlated with each other. PDT downregulated c-Myc in CRC cells, and c-Myc activated the transcription of NEAT1 through the targeting of its promoter region. Within p53mut SW480 cells, PDT failed to alter cell viability and apoptosis but still downregulated c-Myc, NEAT1, and iASPP and upregulated miR-124. In p53 mutant high-abundant CRC tissues, c-Myc and NEAT1 were up-regulated, and miR-124 was downregulated. In c-Myc high-abundant CRC tissues, NEAT1 and iASPP were up-regulated, and miR-124 was downregulated. The critical role of the c-Myc/NEAT1 axis in mediating CRC response to PDT treatment via the miR-124/iASPP/p53 feedback loop was conclusively demonstrated.
Highlights
Colorectal cancer is the most common digestive tract malignancy that originates from the colorectal mucosa
Within the c-Myc/NEAT1 Involved in Photodynamic therapy (PDT) Treatment subcutaneously implanted tumor model, NEAT1 silencing promoted the suppressive roles of PDT in tumor growth
NEAT1 silencing enhanced, whereas miR-124 inhibition attenuated PDT effects on cancer cases (CRC) cells; miR-124 inhibition significantly reversed the roles of NEAT1 silencing in PDT-treated CRC cells
Summary
Colorectal cancer is the most common digestive tract malignancy that originates from the colorectal mucosa. Late clinical diagnoses in the middle and advanced stages deny the patients of their best window for successful tumor treatment through the trifecta of surgery, chemotherapy, and radiotherapy. Since PDT was listed as the primary therapy for tumor treatment in 1997, the single utilization of PDT or its combination with surgery, radiotherapy, and chemotherapy was extensively employed in the treatment of malignancies [5,6,7]. Previous reports indicate that the miR-124/iASPP/p53 feedback loop exerted a substantial effect on PDT resistance of CRC cells [11]. Considering that miR-124/ iASPP/p53 feedback loop played a vital role in the PDT resistance of CRC cells, its related mechanisms were subsequently studied
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