Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis

Daolin Ji; Li Hou; Chunyang Xie; Haonan Feng; Dongdong Bao; Yue Teng; Junhao Liu; Tiangang Cui; Xiuhong Wang; Yi Xu; Gang Tan

doi:10.1155/2022/3855462

Deoxyelephantopin Suppresses Pancreatic Cancer Progression In Vitro and In Vivo by Targeting linc00511/miR-370-5p/p21 Promoter Axis

J Oncol. 2022 Jun 25:2022:3855462. doi: 10.1155/2022/3855462. eCollection 2022.

Authors

Daolin Ji^{1

2}, Li Hou¹, Chunyang Xie¹, Haonan Feng¹, Dongdong Bao¹, Yue Teng¹, Junhao Liu¹, Tiangang Cui¹, Xiuhong Wang³, Yi Xu^{4

5}, Gang Tan¹

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China.
² The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, China.
³ Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
⁴ Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, China.
⁵ Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.

Abstract

Objectives: Deoxyelephantopin (DET) is a kind of natural active ingredient extracted from the Chinese herbal medicine Elephantopus scaber L. Many studies have revealed the potential antitumor effect on multiple malignancies. However, the detailed mechanism of its antitumor effect in pancreatic cancer remains unclear. Recently, studies have confirmed that noncoding RNA (ncRNA) plays an important regulatory role in malignancies. This research was performed to explore the relationship between ncRNA and DET-induced tumor inhibition in pancreatic cancer.

Methods: Microarray profiling was applied to identify the candidate ncRNAs associated with DET-induced tumor inhibition. Quantitative real-time PCR was used to evaluate the expression of linc00511 in pancreatic cancer cells and tissues. The influence of DET on the cell proliferation, migration, and invasion was assessed by CCK-8, colony formation, wound healing, and Transwell assays. The relationship between lncRNAs, miRNAs, and p21 promoter region was analyzed by bioinformatics and verified by luciferase reporter gene and western blotting. The effect of linc00511 on nuclear translocation of miR-370-5p was explored by cytoplasmic and nuclear RNA purification. Moreover, the effect of DET on tumor growth and metastasis, and the prophylactic effect were investigated by establishing subcutaneous and lung metastatic tumor models.

Results: Microarray assay indicated linc00511 was a potential target gene. The antitumor effect of DET in pancreatic cancer depended on downregulating linc00511 expression, and linc00511 might be an oncogene in pancreatic cancer. Silencing linc00511 enhanced the antitumor function of DET; conversely, linc00511 overexpression antagonized the DET cytotoxic effect. Additionally, miR-370-5p could bind to p21 promoter to exert the RNA activation and then promote p21 expression. P21 was a downstream gene of linc00511 and associated with pancreatic cancer progression. Linc00511 regulated p21 expression by blocking miR-370-5p nuclear translocation.

Conclusions: To sum up, the present finding confirmed that DET suppressed the malignant biological behavior of pancreatic cancer via linc00511/miR-370-5p/p21 promoter axis.