Low expression of lncRNA SBF2‐AS1 regulates the miR‐302b‐3p/TGFBR2 axis, promoting metastasis in laryngeal cancer

Abstract

The 5‐year survival rate of laryngeal cancer continues to decline, and the laryngeal particularity of the anatomy adversely affects the patient's quality of life. Emerging evidence suggests that long noncoding RNAs (lncRNAs) are closely correlated to key steps in the malignant progression of cancer cells. In this study, we report the role of lncRNA SBF2‐AS1/miR‐302b‐3p/TGFBR2 interactions in the metastasis of laryngeal squamous cell carcinoma (LSCC). We verified that SBF2‐AS1 was significantly downregulated in LSCC tissues and cell lines using qRT‐PCR analysis. Its low expression was correlated to lymph node metastasis and an advanced clinical stage. More importantly, LSCC patients with low expression of SBF2‐AS1 tended to have a poor prognosis. Based on this, we performed gain‐of‐function and loss‐of‐function experiments in LSCC cell lines. The results confirmed that knocking down SBF2‐AS1 can promote the metastasis of LSCC cells and enhance epithelial–mesenchymal transition phenotype, while the upregulation of SBF2‐AS1 expression resulted in the opposite. Our in vivo model verified that SBF2‐AS1 overexpression could inhibit LSCC cell metastasis. Subsequent mechanistic studies revealed that SBF2‐AS1 acted as a competing endogenous RNA that upregulated the expression of TGFBR2 by endogenous sponging for miR‐302b‐3p in LSCC cell lines. Moreover, miR‐302b‐3p overexpression reversed the inhibitory effects on LSCC metastasis induced by upregulation of SBF2‐AS1 expression, and inhibition of TGFBR2 expression reversed the effect of SBF2‐AS1 on metastasis. Our study proposes SBF2‐AS1 as a biomarker to predict the prognosis of LSCC patients and a novel potential therapeutic target.

Diagnostic and Prognostic Value of microRNAs in Patients with Laryngeal Cancer: A Systematic Review

“…Of those, 166 were excluded for describing HNSCC cases without focus on the larynx ( n = 28), for being exclusively in vitro studies ( n = 39), for having a number of patients less than 10 or for using patient data from public databases ( n = 50), for not quantifying miRNAs in patient samples ( n = 43) and for other reasons, such as for not having statistically significant results or wrong miRNA sequence ( n = 6). Finally, the review was performed on a total of 177 studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 …”

Identification of a seven-lncRNAs panel that serves as a prognosis predictor and contributes to the malignant progression of laryngeal squamous cell carcinoma

“…In addition, the high expression of LINC01194 has been shown to be negatively correlated with the clinical outcome of LSCC patients (37). Moreover, the low expression of lncRNA SBF2-AS1 was correlated to lymph node metastasis, advanced clinical stage, as well as poor prognosis of LSCC (38) these findings, no lncRNA biomarker was used to predict the prognosis of LSCC clinically. Hence, identifying more lncRNA biomarkers with high specificity for evaluating LSCC progression and prognosis is needed.…”

Unboxing the network among long non-coding RNAs and TGF-β signaling in cancer

“…Higher CASC18 expression was associated with the status of occult lymph node metastasis in TSCC cohorts, but it was not discussed how its expression could be modulated. Moreover, the lncRNA SBF2 antisense RNA 1 ( SBF2 - AS1 ) was proposed to sponge miR - 302b - 3p , upregulating TGFBR2 expression in laryngeal SCC cells ( 42 ). Of note, considering the key role of TGF-β signaling in promoting EMT in laryngeal SCC cells ( 43 ), and since SBF2-AS1 could induce TGFBR2 expression, it would be expected that this lncRNA could enhance EMT.…”