Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO.
This study aimed to investigate the role of long noncoding RNAs (lncRNAs) in the metastasis of colorectal cancer (CRC). Metastasis is an important prognostic factor of CRC, and lncRNAs have been implicated in tumor proliferation and metastasis. The human CRC cell lines HCT116, HT29, SW480, DLD-1, and SW620 were used in the study. Genome-wide lncRNA expression patterns in metastatic lymph nodes compared with paired normal lymph nodes of CRC were assessed by microarray analysis. Gastric adenocarcinoma predictive long intergenic noncoding (GAPLINC) RNA was detected via functional prediction. The increased expression of GAPLINC was found to be positively correlated with larger tumor size, advanced tumor stage (T stage), advanced node stage (N stage), increased death, and shorter survival of patients with CRC by in situ hybridization analysis. Besides, the decreased expression of GAPLINC could significantly repress CRC cell invasion in vitro and also inhibit proliferation in vitro and in vivo. RNA pull-down with mass spectrum experiments revealed that PTB-associated splicing factor (PSF) and non-POU-domain-containing octamer-binding (NONO) protein bound to GAPLINC and reversed the effect of GAPLINC on cell invasion. Gene array and bioinformatics analyses identified that snail family zinc finger 2 (SNAI2) was involved in the biological processes of GAPLINC/PSF/NONO. This study indicated the importance of GAPLINC in promoting CRC invasion via binding to PSF/NONO and partly by stimulating the expression of SNAI2. Hence, GAPLINC may serve as a promising target for CRC diagnosis and therapy. The findings may help in developing a novel therapeutic strategy for patients with CRC.
The Second Clinical Medical College of Nanjing Medical University, Nanjing, China.
Peng
P
Yang
The Second Clinical Medical College of Nanjing Medical University, Nanjing, China.
Tao
T
Chen
The Second Clinical Medical College of Nanjing Medical University, Nanjing, China.
Zipeng
Z
Xu
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Hua
H
Zhu
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jie
J
Wang
The Second Clinical Medical College of Nanjing Medical University, Nanjing, China.|Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Zhenyu
Z
He
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D000072670:PTB-Associated Splicing Factor / Q000378:metabolism*; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D046888:Tissue Array Analysis; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D000072670:PTB-Associated Splicing Factor; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C000604408:SNAI2 protein, human; D000071250:Snail Family Transcription Factors
GAPLINC; NONO; PSF; colorectal cancer; long noncoding RNA