Long Noncoding RNA SNHG16 Promotes Cell Proliferation by Sponging MicroRNA-205 and Upregulating ZEB1 Expression in Osteosarcoma

Abstract

Background/Aims: Long noncoding RNAs (lncRNAs) have been a research hotspot, as they play important roles in tumor development. However, their expression pattern and biological function in osteosarcoma have not yet been clarified. Methods: Differentially expressed lncRNAs in osteosarcoma and paracarcinoma tissues were identified by screening an lncRNA microarray, and candidate lncRNAs were verified by quantitative real-time PCR (qRT-PCR). A series of bioinformatics and molecular biological methods were adopted to investigate the interaction among lncRNA, microRNA (miRNA), and miRNA target genes during the development and occurrence of osteosarcoma. Cell viability was measured using a Cell Counting Kit-8 assay. Results: Chip microarray screening combined with the validation of differentially expressed candidate lncRNAs showed that the lncRNA small nucleolar RNA host gene 16 (SNHG16) had the largest fold change. SNHG16 was highly expressed in osteosarcoma tissues and cell lines, and its downregulation led to the suppressed proliferation of osteosarcoma cells. Further investigations revealed that SNHG16 could upregulate zinc finger E-box-binding homeobox 1 (ZEB1) expression by acting as an endogenous sponge of miR-205. Moreover, rescue assays proved that the effects of SNHG16 on the proliferation of osteosarcoma cells were dependent on miR-205. Conclusion: SNHG16 can significantly enhance the proliferation of osteosarcoma cells. In addition, SNHG16, miR-205, and ZEB1 interact in a common pathway during the development and occurrence of osteosarcoma, providing novel targets for intervention in the treatment of osteosarcoma.

Up‐regulation of SNHG16 induced by CTCF accelerates cardiac hypertrophy by targeting miR‐182‐5p/IGF1 axis

“…For example, SNHG16 facilitates cell proliferation via activating WNT signaling pathway in esophageal squamous cell carcinoma (ESCC) (Han et al, 2018). SNHG16 upregulates ZEB1 expression to drive osteosarcoma cell proliferation via sponging miRNA‐205 (Zhu et al, 2018). In addition, a previous study has revealed that SNHG16 as a ceRNA facilitates lipopolysaccharides‐induced acute pneumonia through miR‐370‐3p/IGF2 axis (Zhang et al, 2020).…”

<p><em>SNHG16</em>: A Novel Long-Non Coding RNA in Human Cancers</p>

“…30 SNHG16 was also overexpressed in human osteosarcoma tissues and cell lines when compared to matched normal tissues and cell lines, respectively. 16,[36][37][38][39] Osteosarcoma patients with high SNHG16 expression are more likely to have shorter survival, larger tumors, more advanced TNM stage, metastasis, and poorer prognosis. 37,39 Zhou et al revealed that high expression of SNHG16 was associated with poor clinical pathological parameters and shorter OS and progression-free survival, which indicated that it can act as an independent prognostic factor of glioma.…”

“…However, in osteosarcoma, mechanistic investigations revealed that SNHG16 could act as a sponge for miR-98-5p, miR-1301, miR-16, miR-340, and miR-205. 16,[36][37][38][39] Inhibition of miR-98-5p and miR205 increases zinc finger E-box binding homeobox 1 (ZEB1), E2F transcription factor 5 (E2F5), and STAT3 expression to promote tumorigenesis. 36,37 Li et al reported that SNHG16 was revealed to bind with miR-200a-3p, leading to the proliferation of CRC cells.…”

“…16,[36][37][38][39] Inhibition of miR-98-5p and miR205 increases zinc finger E-box binding homeobox 1 (ZEB1), E2F transcription factor 5 (E2F5), and STAT3 expression to promote tumorigenesis. 36,37 Li et al reported that SNHG16 was revealed to bind with miR-200a-3p, leading to the proliferation of CRC cells. 31 Zhou et al found that SNHG16 regulated proliferation and invasion of glioma cells through the miR-373/epidermal growth factor receptor (EGFR) axis by the phosphatidylinositol 3-kinase (PI3K) -protein kinase B (AKT) pathway.…”

Commentary on: The potency of lncRNA MALAT1/miR-155 in altering asthmatic Th1/Th2 balance by modulation of CTLA4

“…Researchers showed that lnc RNA could alter gene expression by modifying the effects of other non-coding RNA, such as miRNA [4]. Studies suggest that lncRNA modulates miRNA function by acting as a sponge to absorb the miRNA and prevent it from degrading its mRNA target [5,6]. Alternatively, lncRNA may antagonize the actions of miRNA by competing with them for binding to their mRNA targets [7].…”