Yan Li1, Dongdong Li1, Mei Zhao1, Shengkai Huang2, Qiao Zhang1, Hong Lin1, Wenjie Wang1, Kexin Li1, Zihao Li1, Weiyan Huang3, Yiqun Che4, Changzhi Huang5. 1. Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Beijing 100021, China. 2. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. 3. Department of Veterinary Biosciences, Ohio State University, Columbus, OH 43210, USA. Electronic address: huang.2067@osu.edu. 4. Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Electronic address: cyq@cicams.ac.cn. 5. Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China; Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Beijing 100021, China. Electronic address: huangcz@cicams.ac.cn.
Abstract
AIMS: Increasing evidence suggests that long noncoding RNAs act as critical regulators in various malignancies. Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of human cancers. The present study aims to investigate the molecular mechanism through which SNHG6 promotes the development of gastric cancer (GC). MAIN METHODS: The expression level of SNHG6 in human serum was examined using reverse transcription and quantitative polymerase chain reaction (qRT-PCR). RNA- fluorescence in situ hybridization (FISH) and Cell nucleus/cytoplasm fraction isolation assay were used to detect the cellular distribution of SNHG6. Senescence-associated β-galactosidase (SA-β-gal) activity assay was performed to detect cell senescence. BALB/c male nude mice were used to establish the xenograft model. KEY FINDINGS: We found that SNHG6 was up-regulated in human GC tissues and serum. Knockdown of SNHG6 inhibited GC cell proliferation, induced cellular senescence, and reduced xenograft tumor growth in BALB/c nude mice. Knockdown of SNHG6 stimulated p21 expression and the tumor-suppressive effect of SNHG6 in GC cells was dependent on p21. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. SIGNIFICANCE: Our findings show that SNHG6 knockdown inhibits GC development by upregulating p21; this effect is dependent on the activation of the JNK pathway and suppression of EZH2 expression. This study indicates that SNHG6 plays an important role in GC progression via the regulation of 21.
AIMS: Increasing evidence suggests that long noncoding RNAs act as critical regulators in various malignancies. Small nucleolar RNA host gene 6 (SNHG6) plays a role in the progression of humancancers. The present study aims to investigate the molecular mechanism through which SNHG6 promotes the development of gastric cancer (GC). MAIN METHODS: The expression level of SNHG6 in human serum was examined using reverse transcription and quantitative polymerase chain reaction (qRT-PCR). RNA- fluorescence in situ hybridization (FISH) and Cell nucleus/cytoplasm fraction isolation assay were used to detect the cellular distribution of SNHG6. Senescence-associated β-galactosidase (SA-β-gal) activity assay was performed to detect cell senescence. BALB/c male nude mice were used to establish the xenograft model. KEY FINDINGS: We found that SNHG6 was up-regulated in human GC tissues and serum. Knockdown of SNHG6 inhibited GC cell proliferation, induced cellular senescence, and reduced xenograft tumor growth in BALB/c nude mice. Knockdown of SNHG6 stimulated p21 expression and the tumor-suppressive effect of SNHG6 in GC cells was dependent on p21. Furthermore, the activation of the c-Jun N-terminal kinase (JNK) pathway and the decrease in Enhancer of Zeste Homolog 2 (EZH2) expression levels represented two mutually independent mechanisms by which SNHG6 knockdown resulted in the upregulation of p21. SIGNIFICANCE: Our findings show that SNHG6 knockdown inhibits GC development by upregulating p21; this effect is dependent on the activation of the JNK pathway and suppression of EZH2 expression. This study indicates that SNHG6 plays an important role in GC progression via the regulation of 21.
Authors: Narasimha M Beeraka; Hao Gu; Nannan Xue; Yang Liu; Huiming Yu; Junqi Liu; Kuo Chen; Vladimir N Nikolenko; Ruitai Fan Journal: Exp Biol Med (Maywood) Date: 2022-01-22