Zhao Wang1, Zhimin Liu2, Xiaojie Fang1, Han Yang3. 1. Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. 2. Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China. 3. Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in Southern China, and Collaborative Innovation Center of Cancer Medicine Guangzhou, Guangzhou, China.
Abstract
BACKGROUND/AIMS: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. METHODS: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo). The fluorescence ratios of cell viability were recorded using a multi-plate reader (Synergy 2, BioTek, Winooski, VT, USA) and the colonies were counted using an ELIspot Bioreader 5000 (BIO-SYS, Karben, GE). RESULTS: MiR-142-5p was significantly downregulated in non-small cell lung cancer tissue and cell lines compared to normal human lung tissues. Overexpression of miR-142-5p resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-142-5p overexpression markedly suppressed cell proliferation in vitro and in vivo. Conversely, inhibition of miR-142-5p promoted lung cancer growth. Mechanistic studies showed that PIK3CA was a potential target of miR-142-5p and it mediated reduction of PIK3CA resulting in suppression of PI3K/Akt pathway. CONCLUSIONS: Our results demonstrate that miR-142-5p functions as a growth suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in non-small cell lung cancer.
BACKGROUND/AIMS: Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating lung cancer growth and progression are not fully identified yet. METHODS: In this study, the expression of miR-142-5p was measured in non-small cell lung cancer tissue and cell lines by qRT-PCR. The functional assays including the cell viability, colony formation, cell migration and invasion were performed in miR-142-5p mimic or inhibitor transfected cell lines (in vitro) and the cell tumorigenesis in nude mice (in vivo). The fluorescence ratios of cell viability were recorded using a multi-plate reader (Synergy 2, BioTek, Winooski, VT, USA) and the colonies were counted using an ELIspot Bioreader 5000 (BIO-SYS, Karben, GE). RESULTS:MiR-142-5p was significantly downregulated in non-small cell lung cancer tissue and cell lines compared to normal human lung tissues. Overexpression of miR-142-5p resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-142-5p overexpression markedly suppressed cell proliferation in vitro and in vivo. Conversely, inhibition of miR-142-5p promoted lung cancer growth. Mechanistic studies showed that PIK3CA was a potential target of miR-142-5p and it mediated reduction of PIK3CA resulting in suppression of PI3K/Akt pathway. CONCLUSIONS: Our results demonstrate that miR-142-5p functions as a growth suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in non-small cell lung cancer.
Authors: Fu Yang; Wan Jun Zhao; Cong Li Jia; Xiao Kai Li; Qiang Wang; Zi Li Chen; De Quan Jiang Journal: Am J Cancer Res Date: 2018-04-01 Impact factor: 6.166