Jin-Hui Zhu1, Ramon Andrade De Mello2, Qiu-Liang Yan3, Jian-Wei Wang4, Yan Chen5, Qing-Huang Ye5, Zhi-Jiang Wang5, Hai-Jun Tang6, Tao Huang7. 1. Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: 2512016@zju.edu.cn. 2. Department of Biomedical Sciences & Medicine, University of Algarve, Faro, Portugal. 3. Department of General Surgery, Jinhua People's Hospital, Jinhua 321000, China. 4. Department of Surgical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. 5. Department of General Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. 6. Department of General Surgery, Shaoxing People's Hospital, Shaoxing 312000, China. Electronic address: tanghaijun.1988@163.com. 7. Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: tohuangtao@126.com.
Abstract
OBJECTIVE: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC. METHODS: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity. RESULTS: MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANC tumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression. CONCLUSION: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANC patients.
OBJECTIVE:Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. The study aimed to investigate the effects and molecular mechanism of miR-139-5p/SLC7A11 on the proliferation and metastasis of PANC. METHODS: Bioinformatics was used to analyze the differentially expressed genes in the TCGA database. PANC cell lines with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and have been used to detect cell proliferation, invasion and metastasis of PANC Subsequently, bioinformatic analysis and dual luciferase reporter assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mice model was used to explore the functions of miR-139-5p in PANC tumorigenicity. RESULTS:MiR-139-5p could regulate and affect the protein expression of P13K and Akt associated with phosphatidylinositol signaling pathway by inhibiting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, invasion and metastasis could be inhibited by miR-139-5p overexpression and be promoted by SLC7A11 overexpression. MiR-139-5p overexpression could suppress PANCtumor growth and the expressions of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibitory of miR-139-5p to PANC cell proliferation, invasion and metastasis was partly due to its inhibiting effect on SLC7A11 expression. CONCLUSION: Our study proves that miR-139-5p/SLC7A11 has important functions on PANC, suggesting that miR-139-5p can be used as a biomarker for PANCpatients.
Authors: Zijian Wu; Jin Xu; Chen Liang; Qingcai Meng; Jie Hua; Wei Wang; Bo Zhang; Jiang Liu; Xianjun Yu; Si Shi Journal: Clin Transl Med Date: 2021-03