NEAT1_2—SFPQ axis mediates cisplatin resistance in liver cancer cells in vitro

Abstract

Yi Ru,1–4 Xiao-Jie Chen,5 Wen-Zhi Guo,1–4 She-Gan Gao,5 Yi-Jun Qi,5 Pan Chen,5 Xiao-Shan Feng,5 Shui-Jun Zhang1–4 1Henan Key Laboratory of Digestive Organ Transplantation, 2Open Laboratory of Key Disciplines of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation, 3Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplant Medicine, 4Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 5Henan Key Laboratory of Cancer Epigenetics; Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, People’s Republic of China Background: Liver cancer is a type of malignant tumor with high morbidity and mortality in People’s Republic of China. Its occurrence and development involve the variation and expression changes of multiple genes, and the pathogenesis and related regulatory networks are complex. Purpose: In the present research, we investigate the involvement of NEAT1_2 and SFPQ in cisplatin resistance in liver cancer. The effects of LncRNA NEAT1 and SFPQ expression on the chemotherapeutic resistance of liver cancer cells were analyzed. Methods: The expression level of NEAT1_2 and SFPQ mRNA in tissue specimens or cell lines were examined by RT-qPCR and western blotting. CCK-8 assay was performed to evaluate cell viability. Cell proliferation was performed using the EdU cell proliferation assay. Results: Our data showed that increase NEAT1_2 and SFPQ expressions in liver cancer specimens were associated with the development of cisplatin resistance; high SFPQ expression level impaired patients’ survival from liver cancer. Gain-and loss-of function assay using NEAT1_2 knock-in and knock-out cells constructed using CRISPER/Cas9 system revealed that NEAT1_2 is essential for liver cancer cell survival and mediates cisplatin resistance in liver cancer cells at least partially through SFPQ. Artificial change in NEAT1_2 expression level didn’t significantly influence SFPQ transcription or translation level. Conclusion: Our data revealed NEAT1_2—SFPQ axis as a novel cisplatin resistance mechanism in liver cancer cells in vitro. Keywords: NEAT1, NEAT1_1, NEAT1_2, SFPQ, liver cancer, cisplatin resistance

Keywords

• NEAT1
• NEAT1_1
• NEAT1_2
• SFPQ
• liver cancer
• cisplatin resistance.