Depletion of CPNE7 sensitizes colorectal cancer to 5‐fluorouracil by downregulating ATG9B expression

• Published in: Journal of cellular and molecular medicine 2024-04, Vol.28 (8), p.e18261-n/a
• Main Authors: Xu, Weile, Tang, Yujie, Yang, Yang, Wang, Changjing, Liu, Chen, Zhang, Jianqing, Zhao, Lianmei, Wang, Guiying
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Antibodies; Apoptosis; ATG9B; Autophagy; Autophagy-Related Proteins - genetics; Autophagy-Related Proteins - metabolism; Biomarkers; Cancer therapies; Carcinogenesis - genetics; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell proliferation; Cell Proliferation - genetics; Cell Transformation, Neoplastic - genetics; Chemoresistance; chemosensitivity; Chemotherapy; Colonies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; CPNE7; Fluorouracil - pharmacology; Fluorouracil - therapeutic use; Gene expression; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Humans; Infections; Infrared imaging systems; Medical prognosis; Membrane Proteins - genetics; Metastasis; Original; Phagosomes; Proteins; Rapamycin; Transcriptomes; Transmission electron microscopy; Tumorigenesis; Western blotting
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.18261

We aimed to explore the biological function of CPNE7 and determine the impact of CPNE7 on chemotherapy resistance in colorectal cancer (CRC) patients. According to the Gene Expression Profiling Interactive Analysis database and previously published data, CPNE7 was identified as a potential oncogene in CRC. RT‐qPCR and Western blotting were performed to verify the expression of CPNE7. Chi‐square test was used to evaluate the associations between CPNE7 and clinical features. Cell proliferation, colony formation, cell migration and invasion, cell cycle and apoptosis were assessed to determine the effects of CPNE7. Transcriptome sequencing was used to identify potential downstream regulatory genes, and gene set enrichment analysis was performed to investigate downstream pathways. The effect of CPNE7 on 5‐fluorouracil chemosensitivity was verified by half maximal inhibitory concentration (IC50). Subcutaneous tumorigenesis assay was used to examine the role of CPNE7 in sensitivity of CRC to chemotherapy in vivo. Transmission electron microscopy was used to detect autophagosomes. CPNE7 was highly expressed in CRC tissues, and its expression was correlated with T stage and tumour site. Knockdown of CPNE7 inhibited the proliferation and colony formation of CRC cells and promoted apoptosis. Knockdown of CPNE7 suppressed the expression of ATG9B and enhanced the sensitivity of CRC cells to 5‐fluorouracil in vitro and in vivo. Knockdown of CPNE7 reversed the induction of the autophagy pathway by rapamycin and reduced the number of autophagosomes. Depletion of CPNE7 attenuated the malignant proliferation of CRC cells and enhanced the chemosensitivity of CRC cells to 5‐fluorouracil.