LncRNA HOTTIP inhibits cell pyroptosis by targeting miR‐148a‐3p/AKT2 axis in ovarian cancer

• DOI: 10.1002/cbin.11588
• Publication Date: 2021-03-12T10:32:25Z
• Authors: Cai Tan; Wei Liu; Zhi‐Hua Zheng; Xiao‐Gang Wan
• Keywords: Ovarian Neoplasms; 0301 basic medicine; 3. Good health; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Line, Tumor; Pyroptosis; Humans; Female; RNA, Long Noncoding; Proto-Oncogene Proteins c-akt; Cell Proliferation

AbstractLong noncoding RNA HOTTIP is a crucial regulator in multiple types of cancer, including ovarian cancer (OC). However, the biological roles and underlying mechanisms of HOTTIP in OC have rarely been studied. Hence, this study aimed to investigate the functional correlation between HOTTIP and pyroptosis in OC progression. The expression of HOTTIP in OC tissues and cell lines was characterized by quantitative real‐time PCR. Cell proliferation was evaluated using Cell Counting Kit‐8 and clone formation assays. Western blot was performed to quantify protein levels. A dual‐luciferase reporter assay was used to analyze the molecular interaction among HOTTIP, miR‐148a‐3p, and AKT2. The expression of HOTTIP was significantly upregulated in OC tissue samples and cell lines. The silencing of HOTTIP led to the inhibition of cell proliferation and NLRP1 inflammasome‐mediated pyroptosis. In addition, HOTTIP increased AKT2 expression by negatively regulating miR‐148a‐3p and then inhibited ASK1/JNK signaling. Further rescue experiments revealed that downregulation of miR‐148a‐3p and overexpression of AKT2 obviously diminished the effects of HOTTIP downregulation in OC cells. Thus, our study elucidated a novel pyroptosis‐related mechanism by which HOTTIP participated in OC progression, which might provide a theoretical reference for clinical treatment.