Silencing of LncRNA SNHG16 Downregulates Cyclin D1 (CCND1) to Abrogate Malignant Phenotypes in Oral Squamous Cell Carcinoma (OSCC) Through Upregulating miR-17-5p

Abstract

Background Targeting the long non-coding RNAs (LncRNAs)-microRNAs (miRNAs)-mRNA competing endogenous RNA (ceRNA) networks has been proved as an effective strategy to treat multiple cancers, including oral squamous cell carcinoma (OSCC). Based on this, the present study identified a novel LncRNA SNHG16/miR-17-5p/CCND1 signaling pathway that played an important role in regulating the pathogenesis of OSCC. Methods The expression levels of cancer-associated genes were examined by Real-Time qPCR and Western Blot at transcriptional and translated levels, respectively. CCK-8 assay was performed to determine cell proliferation, and cell apoptosis ratio was measured by the Annexin V-FITC/PI double staining assay. Transwell assay was performed to examine cell migration, and dual-luciferase reporter gene system assay was used to validate the ceRNA networks. Results LncRNA SNHG16 and CCND1 were upregulated, while miR-17-5p was downregulated in OSCC tissues and cell lines, compared to their normal counterparts. Also, miR-17-5p negatively correlated with both LncRNA SNHG16 and CCND1 mRNA, but LncRNA SNHG16 was positively relevant to CCND1 mRNA in OSCC tissues. By performing the gain- and loss-of-function experiments, we noticed that LncRNA SNHG16 overexpression aggravated the malignant phenotypes, such as cell proliferation, viability, migration and epithelial-mesenchymal transition (EMT) in OSCC cells, while LncRNA SNHG16 knock-down had opposite effects. Furthermore, our dual-luciferase reporter gene system evidenced that LncRNA SNHG16 sponged miR-17-5p to upregulate CCND1 in OSCC cells, and the inhibiting effects of LncRNA SNHG16 ablation on OSCC progression were abrogated by both downregulating miR-17-5p and overexpressing CCND1. Finally, the xenograft tumor-bearing mice models were established, and our data validated that LncRNA SNHG16 served as an oncogene to promote tumorigenicity of OSCC cells in vivo. Conclusion Taken together, targeting the LncRNA SNHG16/miR-17-5p/CCND1 axis hindered the development of OSCC, and this study provided potential diagnostic and therapeutic biomarkers for OSCC in clinic.

Targeting the lncRNA FGD5-AS1/miR-497-5p/PD-L1 Axis Inhibits Malignant Phenotypes in Colon Cancer (CC)

“…Researchers agreed that uncovering the underlying mechanisms of CC pathogenesis will help to cure CC [ 3 ], and emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in regulating CC progression by serving as tumor suppressors or oncogenes [ 4 ]. For example, overexpression of LincC01082 [ 5 ] and LINC00261 [ 6 ] suppressed CC development, while lncRNA CALIC promoted malignant phenotypes in CC cells [ 7 ]. Among all the lncRNAs, we noticed that lncRNA FGD5-AS1 acted as an oncogene to facilitate the development of multiple cancers, such as colorectal cancer (CRC) [ 8 ], oral cancer [ 9 ], non-small-cell lung cancer (NSCLC) [ 10 ], and esophageal squamous cell carcinoma (ESCC) [ 11 ].…”

Identifying Drug Targets of Oral Squamous Cell Carcinoma through a Systems Biology Method and Genome-Wide Microarray Data for Drug Discovery by Deep Learning and Drug Design Specifications

“…There was a significant positive correlation between angiogenesis and apoptosis [ 40 ]. CCND1 was negatively correlated with apoptosis and an accelerated cell cycle [ 41 , 42 ].…”

Impact of Non-Coding RNAs on Chemotherapeutic Resistance in Oral Cancer

“…The expression of lncRNA-PNUTS is elevated and correlates with the mRNA level of ZEB1. A number of lncRNAs have been identified as EMT modulators in oral cancer [ 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 ,…”