Knockdown of SNHG12 suppresses tumor metastasis and epithelial‑mesenchymal transition via the Slug/ZEB2 signaling pathway by targeting miR‑218 in NSCLC

Abstract

Non-small cell lung cancer (NSCLC) is a type of lung cancer which has a high mortality and low survival rate. Previous studies have revealed that long non-coding RNAs participate in tumorigenesis and metastasis in NSCLC. In the present study, the function of small nucleolar RNA host gene 12 (SNHG12) was investigated in NSCLC. Using reverse transcription-quantitative polymerase chain reaction analysis, it was identified that SNHG12 was significantly overexpressed in NSCLC specimens. Furthermore, overexpression of SNHG12 was identified to be associated with tumor progression and poor overall survival rates. Knockdown of SNHG12 in NSCLC cells could effectively induce cell apoptosis and suppress cell viability, proliferation, migration and invasion via inhibition of the epithelial-mesenchymal transition process. Furthermore, a direct interaction between microRNA (miR)-218 and the binding site of SNHG12 was identified. SNHG12 acted as an endogenous sponge for miR-218. Knockdown of SNHG12 upregulated the expression level of miR-218 as well as downregulating the Slug/zinc finger E-box-binding homeobox 2 EMT signaling pathway, and thus inhibited cell migration and invasion. Therefore, SNHG12 may serve as a key biomarker and a potential therapeutic target for the treatment of NSCLC.

Long Noncoding RNA SNHG12 is a Potential Diagnostic and Prognostic Biomarker in Various Tumors

“…There is evidence that lncRNAs can act as molecular scaffolds, sponges or coactivators in tumor scaffolds by interacting with DNA, RNA or proteins [5,31,32] . At present, increasing evidence has shown that the abnormally high expression of SNHG12 plays a carcinogenic role in various malignant tumors [10][11][12][13][14][15][16][17][18][19][26][27][28][29] .…”

“…Liu et al found that inhibition of the SNHG12-miR-195-SOX5 axis signi cantly obstructs the malignant biological behavior of glioma cells [11] . Sun et al noted that lncRNA SNHG12 accelerates the deterioration of patients with ovarian cancer by upregulating SOX4 [12] . Therefore, whether SNHG12 is a biomarker for the detection and treatment of tumors is a growing concern.…”

“…SNHG12 was shown to be an effective diagnostic biomarker in nasopharyngeal carcinoma with a multivariate Cox regression analysis [10] . Furthermore, increasing evidence suggests that overexpression of SNHG12 is linked to a poor prognosis or a high risk of clinicopathological characteristics in osteosarcoma, nasopharyngeal carcinoma, NSCLC, gastric carcinoma, hepatocellular carcinoma, glioma, cervical cancer, colorectal cancer and triple-negative breast cancer [10][11][12][13][14][15][16][17][18][19] . Therefore, this study hopes to evaluate the potential value of SNHG12 as a prognostic molecular marker through the TCGA database and meta-analysis.…”

MicroRNAs as Theranostics Targets in Oral Carcinoma Stem Cells

“…In addition, it has been revealed that miR-218 negatively regulated the IL-6 receptor and JAK3 gene expression in lung cancer cells by directly targeting their 3 -UTR regions, thereby repressing tumor sphere formation and other tumorigenesis features [81]. Another study showed that administration of miR-218-mimic downregulated the expression of Slug and ZEB2 in lung cancer cells [82], but the detailed mechanism still remains unclear. In OSCC, HPV E6-mediated paxillin expression has been shown to promote colony formation and invasion in oral cancer via decreasing miR-218 [83].…”

Snail2 induced E-cadherin suppression and metastasis in lung carcinoma facilitated by G9a and HDACs

“…Reduced E-cadherin expression has been shown to be associated with poorly differentiated and metastatic NSCLC. In NSCLC, knockdown of SNHG12 suppresses tumor metastasis and epithelial-mesenchymal transition via the Snail2/ ZEB2 signaling pathway by targeting miR-218 [10]. It has been reported that NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Snail2 expression [11].…”