CASC15 contributes to proliferation and invasion through regulating miR-766-5p/ KLK12 axis in lung cancer.

Abstract

Long non-coding RNAs (lncRNAs) are key mediators of cancer. The dysregulation of a lncRNA, CASC15, has been linked to several cancers, except lung cancer. Here, the aim of the study was to explore the role and mechanism of CASC15 in lung cancer regulation, with the focus on its interaction with a potential target, microRNA-766-5p (miR-766-5p) and an oncogene, kallikrein-related peptidase 12 (KLK12). Quantitative real-time PCR (qRT-PCR) was used to assess levels of CASC15, miR-766-5p and KLK12 in lung cancer tissues or cells. Western blot analysis was used to detect KLK12 protein expression. Ectopic expression of CASC15 was induced by a lentiviral system. CCK-8 and transwell assays were used to evaluate lung cancer cell proliferation and invasion, respectively. The interaction among CASC15, miR-766-5p and KLK12 was investigated by bioinformatical analysis and luciferase assay. In lung cancer tissue and cells, CASC15 was upregulated, while miR-766-5p was downregulated. Overexpression of CASC15 promoted lung cancer cell proliferation and invasion. A negative correlation was found between CASC15 and miR-766-5p levels. Overexpression of miR-766-6p reversed the cancer-promoting role of CASC15 in lung cancer cells, which was mediated by KLK12. The tumor-promoting role of CASC15 and tumor-suppressing role of miR-766-5p were also validated in vivo in tumor bearing mice, and KLK12 was also shown as an important mediator. CASC15 promotes lung cancer through the miR-766-5p/KLK12 axis, indicating that CASC15 is a potential therapeutic in lung cancer.

• Authors: Yong Bai, Guojun Zhang, Ruirui Cheng, Rui Yang, Heying Chu
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 18 Issue 18 Pg. 2323-2331 (09 2019) ISSN: 1551-4005 [Electronic] United States
• PMID: 31378128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN766 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• KLK12 protein, human
• Kallikreins

Topics

• A549 Cells
• Alveolar Epithelial Cells (metabolism)
• Animals
• Cell Proliferation (genetics)
• Gene Expression Regulation, Neoplastic
• Heterografts
• Humans
• Kallikreins (metabolism)
• Lung Neoplasms (metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness (genetics)
• RNA, Long Noncoding (genetics, metabolism)
• Transfection
• Tumor Burden (genetics)