Abstract
Accumulating evidence suggested the participation of long noncoding RNAs (lncRNAs) in regulating various biological processes so as to affecting cancer progression. However, the functional role of most lncRNAs in colorectal carcer (CRC) is still largely covered. In the present study, we disclosed SNHG14 as a carcinogene in CRC development, as it was low-expressed in normal colon tissues but markedly upregulated in CRC cell lines. Besides, SNHG14 contributed to CRC cell proliferation, motility and EMT in vitro, and inhibition of it confined CRC tumor growth and liver metastasis in vivo. Next, the mechanistic investigations confirmed that SNHG14-promoted CRC progression was mediated by EPHA7, which was negatively regulated by SNHG14 in CRC via an EZH2-dependent way. Importantly, EZH2 was proved as a transcription factor of EPHA7 and functioned as a repressor in EPHA7 transcription by enhancing methylation on EPHA7 promoter. Meanwhile, SNHG14 increased EZH2 expression in CRC via stabilizing its mRNA by interacting with FUS, and via freeing its mRNA from miR-186-5p-induced silence. All in all, our observations demonstrated that SNHG14 serves as a facilitator in CRC through targeting EZH2-repressed EPHA7 by enhancing EZH2 via recruiting FUS and absorbing miR-186-5p, indicating a promising new road for CRC diagnosis and treatment.
Highlights
Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide, with more than one million people diagnosed as CRC annually[1]
In order to further confirm the function of SNHG14 in CRC progression, the loss- and gain-of-function assays were performed respectively after the expression of SNHG14 was silenced in LoVo cells or enhanced in HT-29 cells (Fig. 1c)
SNHG14 is a newly discovered Long noncoding RNAs (lncRNAs) whose tumorigenic role has already been illustrated in gastric cancer[23], clear cell renal cell carcinoma[22], bladder cancer[21], cervical cancer,[20] and non-small cell lung cancer[24], and its antitumor role in glioma has been revealed previously[25]
Summary
Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide, with more than one million people diagnosed as CRC annually[1]. LncRNAs were considered as transcriptional “noise” that had no biological functions[8], amounting studies have uncovered the emerging role of lncRNAs in multiple cellular processes, such as cell differentiation, proliferation, migration, invasion and so on[9,10]. Based on these functions, lncRNAs have been revealed as key modulators in a large number of human diseases[11], including various cancers[12,13,14,15,16]. SNHG5 contributes to CRC cell survival by targeting STAU118
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