Long noncoding RNA GAPLINC promotes invasion in colorectal cancer by targeting SNAI2 through binding with PSF and NONO

Abstract

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.

Upregulated GAPLINC predicts a poor prognosis in bladder cancer patients and promotes tumor proliferation and invasion

“…The wound healing assay and Transwell assays demonstrated that GAPLINC knockdown significantly inhibited the migratory and invasive abilities of bladder cancer cells. These observations may explain why GAPLINC was upregulated in MIBC tissues compared with NMIBC tissues, and were in agreement with the results of other studies (13,14) on gastric cancer and colorectal cancer.…”

“…GAPLINC is associated with poor prognosis of gastric cancer and regulates gastric cancer cells invasiveness (13,22). GAPLINC also interacts with PTB-associated splicing factor (PSF) and non-POU domain-containing octamer-binding (NONO) protein, and ultimately promotes invasion in colorectal cancer (14). However, little is known about the association between GAPLINC and bladder cancer.…”

“…Increasingly, studies have indicated that lncRNAs may be used as potential prognostic biomarkers and therapeutic targets (11,12). Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) has been demonstrated to be aberrantly expressed in gastric and colorectal cancer (13,14). However, the clinical significance and biological functions of GAPLINC in bladder cancer remain unknown.…”

Long Non-coding RNAs and their Role in Metastasis

“…Isoform β interacts with PTENgp1 through RNA-RNA pairing, facilitates PTENgp1 export to the cytoplasm and modulates its stability and sponge activity (134). Function of gastric adenocarcinoma predictive large intergenic noncoding RNA (GAPLINC) is based on a sponge-related and RNA-protein related MOA (135,136). GAPLINC is associated with shorter survival in a subset of patients with gastric cancer, which overexpress this lncRNA (135).…”

Long non‑coding RNA HOTTIP is able to predict poor prognosis in various neoplasms: A meta‑analysis

“…Recently, several studies have revealed that lncRNAs are dysregulated in numerous types of human cancers, including gastric, colorectal, gastric, ovarian, lung and breast cancer (2)(3)(4)(5)(6)(7). Certain lncRNAs have multiple functions in a wide range of biological processes, including proliferation, apoptosis, or cell migration (2,3,6).…”