Yan Qian1, Wei Song2, Xu Wu1, Guowei Hou1, Haixiao Wang1, Xiao Hang1, Tianfang Xia3. 1. Department of Gastric, The Affiliated Huaian N0.1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huaiyin District, Huai'an City, 223300, Jiangsu Province, China. 2. Department of Gastroenterology, The Affiliated Huaian N0.1 People's Hospital of Nanjing Medical University, Huai'an City, 223300, Jiangsu Province, China. 3. Department of Gastric, The Affiliated Huaian N0.1 People's Hospital of Nanjing Medical University, No. 1 Huanghe West Road, Huaiyin District, Huai'an City, 223300, Jiangsu Province, China. TianfangXiaaji@163.com.
Abstract
BACKGROUND: Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple human carcinomas. AIMS: This study aimed to investigate the regulatory effect of DLX6-AS1 in GC progression. METHODS: The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis, aerobic glycolysis, and mitochondrial respiration was assessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated. RESULTS: DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibited cell viability and colony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancy upon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells. CONCLUSIONS: LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.
BACKGROUND:Gastric cancer (GC) is one of the most commonly diagnosed malignancy worldwide. DLX6 antisense RNA 1 (DLX6-AS1) is a long noncoding RNA (lncRNA) that exhibits oncogenic effects on multiple humancarcinomas. AIMS: This study aimed to investigate the regulatory effect of DLX6-AS1 in GC progression. METHODS: The expression of DLX6-AS1 in GC tissues and cell lines was examined. The cell viability, number of clones, and apoptosis, aerobic glycolysis, and mitochondrial respiration was assessed. The effect of DLX6-AS1 on tumor growth in nude mice was also evaluated. RESULTS:DLX6-AS1 was overexpressed in GC tissues and cell lines. DLX6-AS1 knockdown by short hairpin RNA (shRNA) significantly inhibited cell viability and colony formation, and induced apoptosis. DLX6-AS1 silencing impaired aerobic glycolysis but stimulated mitochondrial respiration in GC cells. miR-4290 was confirmed as a downstream target of DLX6-AS1, and their expression levels were inversely correlated. GC cells expressing sh-DLX6-AS1 showed significantly lower level of 3-phosphoinositide-dependent protein kinase 1 (PDK1), a target of miR-4290, compared to cells expressing control shRNA. In addition, the suppressed GC cell malignancy upon DLX6-AS1 knockdown could be prominently reversed by PDK1 overexpression. Meanwhile, PDK1 overexpression enhanced aerobic glycolysis but repressed mitochondrial respiration under sh-DLX6-AS1 treatment. Furthermore, DLX6-AS1 knockdown significantly delayed the tumor growth in a mouse xenograft model inoculated with GC cells. CONCLUSIONS: LncRNA DLX6-AS1 regulated tumor growth and aerobic glycolysis in GC by targeting miR-4290 and PDK1, suggesting DLX6-AS1 might serve as a novel potential therapeutic target for GC treatment from bench to clinic.
Entities:
Keywords:
DLX6-AS1; Gastric cancer; Long noncoding RNA; PDK1; miR-4290; microRNA
Authors: Soudeh Ghafouri-Fard; Sajad Najafi; Bashdar Mahmud Hussen; Aryan R Ganjo; Mohammad Taheri; Mohammad Samadian Journal: Front Cell Dev Biol Date: 2022-02-25