LncRNA SNHG6 promotes proliferation, invasion and migration in colorectal cancer cells by activating TGF-β/Smad signaling pathway via targeting UPF1 and inducing EMT via regulation of ZEB1

Abstract

Background: Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides in length. They drive many important cancer phenotypes through their interactions with other cellular macromolecules including DNA, RNA and protein. Recent studies have identified numerous lncRNAs active in colorectal cancer (CRC). The lncRNA small nucleolar RNA host gene 6 (SNHG6) has been reported to have an oncogenic role in multiple cancers. However, the biological role and mechanism of SNHG6 in the tumorigenesis of CRC has not been reported in-deep.Methods: The Cancer Genome Atlas (TCGA) database and GEO database were used to identify SNHG6 expression in different human cancers and explore the relationship between SNHG6 expression and patient prognosis using Kaplan-Meier method analysis. SNHG6 expression in 77 pairs of clinical CRC tissues and different CRC cell lines were analyzed by quantitative real-time PCR (qRT-PCR). A CCK-8 assay was used to assess cell proliferation, transwell assay to detect the cell metastasis, and tumor growth was investigated with a nude mice model in vivo. Whether UPF1 and ZEB1 are downstream targets of SNHG6 was verified by bioinformatics target gene prediction, qRT-PCR and western blot.Results: TCGA data showed that SNHG6 was significantly upregulated in colorectal cancer samples in comparison with healthy data samples (P < 0.01). CRC patients with high levels of SNHG6 had a significantly shorter overall survival than those with low levels of SNHG6 (P = 0.0162). qRT-PCR confirmed that the expression of SNHG6 was significantly upregulated in CRC tissues and cell lines. Upregulation of SNHG6 expression induced RKO and HCT116 cell proliferation as well as RKO cell metastasis, while downregulation of SNHG6 expression supressed the proliferation and metastasis of RKO cells and tumor growth in vivo. UPF1 was upregulated and ZEB1 was decreased when SNHG6 knockdown, regulating the TGF-β/Smad pathway and inducing EMT respectively.Conclusions: SNHG6 may play an oncogenic role in CRC cells by activating TGF-β/Smad signaling pathway via targeting of UPF1 and inducing EMT via regulating ZEB1. This could be a prognostic biomarker and therapeutic target for CRC.

Long non‐coding RNA SNHG6 promotes the growth and invasion of non‐small cell lung cancer by downregulating miR‐101‐3p

“…Multiple studies have indicated that upregulation of SNHG6 is associated with poor prognosis, lymph node metastasis and TNM stage in patients with ESCC, CRC and HCC, but its expression has been shown to be downregulated in CRC . SNHG6 is also upregulated in lung adenocarcinoma (LUAD) and positively associated with TNM stage and tumor size in LUAD patients .…”

“…Small nucleolar RNA host gene 6 (SNHG6) is a long non‐coding RNA (lncRNA) which plays a critical role in cancer progression. Increasing data have indicated that the elevated expression of SNHG6 is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), facilitates the cycle progression in breast cancer and promotes cell proliferation and invasion in colorectal cancer (CRC), osteosarcoma, gastric cancer and hepatocellular carcinoma (HCC) . These studies suggest that SNHG6 may be a prognostic factor for cancer.…”

Prognostic and clinicopathological significance of SNHG6 in human cancers: a meta-analysis

“…The small nucleolar RNA host gene 6 (SNHG6; also termed U87HG), a subclass of lncRNA molecules, pervasively participates in gene modulation through functioning as an oncogene in different human cancers, including colorectal cancer [10][11][12][13][14], glioma [15], osteosarcoma [16], breast cancer [17], ovarian cancer [18], lung adenocarcinoma [19], oesophageal cancer [20], gastric cancer [21] and liver cancer [22]. Studies have proven that the upregulation of SNHG6 plays multiple critical roles in cell differentiation, proliferation, apoptosis, and multidrug resistance [23,24]. Currently, despite diverse articles that unveil the link between SNHG6 and cancers, the prognostic value remains contradictory or inconclusive, which may be attributed to limited sample size and methodology.…”

Data_Sheet_1.docx

“…Total RNA extraction, reverse transcription, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed as previously described (10). The sequences of the primers used were as follows: PKM1 mRNA (sense):…”

“…Data in AnnoLnc showed that the expression of SNHG6 in CRC was relatively high compared with that of many other tumors (Figure 2A), while SNHG6 was found to be mainly distributed in the cytoplasm of CRC cells based on the lncLocator and part of the nucleus (6). The differential expression of SNHG6 between CRC and normal tissues was analyzed using ULCAN (10) and Hong statistics in Oncomine, which found a relatively high expression of SNHG6 in CRC that was statistically different (Figures 2B-D). GSE81861, which contains single-cell sequencing data of CRC, was obtained from the GEO database to determine the SNHG6 expression in 272 CRC single cells and 160 normal colorectal cells, which found that SNHG6 was highly expressed in CRC (Figure 2E).…”