Silencing of SNHG6 induced cell autophagy by targeting miR-26a-5p/ULK1 signaling pathway in human osteosarcoma

Abstract

Background lncRNAs have been proved to play crucial parts in various human cytopathology and cell physiology, including tumorigenesis. Down-regulated lncRNAs SNHG6 have shown great cell proliferation inhibitory effects in cancer development. Here we investigated how SNHG6 effected human osteosarcoma (OS) development and progression. Methods: Reverse transcription-quantitative PCR was performed to detect SNHG6 mRNA level in both OS tissues and cell lines. MTT and colony formation assays were used to determine the growth impact of SNHG6. Wound healing and trans-well assay were performed to measure the invasion effect of SNHG6. Western blotting were utilized to dissect molecular mechanisms. Results We identified SNHG6 as a lncRNAs that significantly up-regulated in OS tissues and cells, patients with high SNHG6 expression suffered more malignant metastasis and shorter survival times. Furthermore, silencing of SNHG6 in OS significantly inhibited OS cell growth, weakened cell invasion capacity, arrested cell cycle at G0/G1 phase, and induced cell apoptosis. Additionally, mechanism assays suggested that SNHG6 could competitively sponging miR-26a-5p thereby regulating ULK1, and induced cell apoptosis and autophagy by targeting caspase3 and ATF3. Conclusions: Our findings demonstrated that SNHG6 acted as an oncogene in osteosarcoma cells through regulating miR-26a-5p/ULK1 at a post-transcriptional level. SNHG6 might serve as a candidate prognostic biomarker and a target for novel therapies of osteosarcoma patients.

Long noncoding RNA SNHG6 promotes proliferation and angiogenesis of cholangiocarcinoma cells through sponging miR-101-3p and activation of E2F8

“…overexpressed SNHG6 reduces cell apoptosis but promotes cell cycle, cell migration, invasion, EMT, and chemoresistance. SNHG6 exerts its function mainly by serving as miRNA sponge to antagonize the connections between multiple tumor suppressor miRNAs and their target mRNAs [19][20][21][22][23] . In this study, we analyzed public database and found that SNHG6 was also upregulated in CCA cell lines and tissues, and functional investigations showed that SNHG6 silencing inhibited cell proliferation, migration, and HUVECs tube formation, which indicated that SNHG6 functioned as an oncogene in CCA.…”

<p>Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22</p>

“…In recent years, studies have found that the abnormal expression of circular RNA (circRNA) is involved in the occurrence and development of a variety of tumors, and is expected to become a new target for tumor diagnosis and treatment. 4,5 CircRNA is a closed, circular non-coding RNA molecule formed by covalent bonding between the 3ʹ end and the 5ʹ end by reverse splicing. It is widely present in organisms and is more stable than linear RNA.…”

MicroRNAs play an essential role in autophagy regulation in various disease phenotypes

“…Sphingosine kinase 1 (SPHK1), as a cytosolic enzyme, maintains the intracellular sphingolipid balance and plays vital roles in cell growth, invasion, and autophagy. MicroRNA‐506‐3p initiates mesenchymal‐to‐epithelial transition and suppresses autophagy in osteosarcoma cells by directly targeting SPHK1 (Table ) …”

“…MicroRNA-506-3p initiates mesenchymal-toepithelial transition and suppresses autophagy in osteosarcoma cells by directly targeting SPHK1 (Table 1). 102…”