Abstract
Objective The purpose of this study was to study the effects of the GAS5/microRNA-10b (miR-10b) axis on proliferation, migration, and apoptosis of colorectal cancer (CRC). Methods The expression levels of GAS5 and miR-10b in CRC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing experiment was used to detect the effects of GAS5 and miR-10b on the migration of CRC cells. The luciferase reporter gene experiment was used to verify miRNA targets. Immunohistochemical assay was used to detect the expression of proteins related to metastasis and apoptosis in tumor tissues. Results The expression of GAS5 was downregulated in CRC tissues and cell lines. The overexpression of GAS5 can inhibit cell proliferation and progression, induce apoptosis in vitro, and inhibit the growth of CRC tumor in vivo. In contrast, the expression of miR-10b, a downstream target of GAS5, was increased in CRC tissues and cells. Suppression of the miR-10b gene can inhibit proliferation and metastasis and cause apoptosis of CRC cells. In addition, luciferase reports show that GAS5 inhibits the progression of CRC cells by binding to miR-10b. Rescue experiments showed that overexpressed miR-10b could reverse GAS5-mediated antitumor effect on CRC cells in vivo and in vitro. Conclusions LncRNA GAS5 interacts with miR-10b to inhibit cell proliferation and migration and induces apoptosis in colorectal cancer. GAS5 and miR-10b could become potential therapeutic targets for CRC.
Highlights
Colorectal cancer (CRC) is one of the most frequently diagnosed malignant tumors in the world [1]
The expression of GAS5 was detected in 50 surgical specimens by quantitative real-time polymerase chain reaction (qRT-PCR). the expression level of GAS5 in cancer tissues was lower than that in normal tissues adjacent to cancer (p < 0:05, Figure 1(a)), and the expression level of GAS5 in CRC cell lines SW480 and HCT116 was significantly downregulated compared with that in normal colon epithelial cells NCM460 (p < 0:01, Figure 1(b))
Kaplan Meier (KM) curve results showed that patients with low expression of GAS5 had poor prognosis (Figure 1(c))
Summary
Colorectal cancer (CRC) is one of the most frequently diagnosed malignant tumors in the world [1]. Some LncRNAs with a size of more than 90 kb are known as microRNAs (miRNAs). More and more evidence show that LncRNAs are involved in all aspects of cell physiology and are very important for the occurrence, development, and metastasis of cancer [5]. Several studies have shown that GAS5 is downregulated and plays a role as a tumor suppressor gene in breast cancer [7], ovarian cancer [8], hepatocellular carcinoma [9], and CRC [10]. MiRNAs are small endogenous noncoding RNA molecules (about 22 nt), which play an important role in gene expression and can promote translation inhibition or degradation [12]. Among several candidate miRNAs that regulate cell progression, a large amount of evidence has reported that the expression of microRNA-10b (miR-10b)
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