SNHG6 facilitates the epithelial-mesenchymal transition and metastatic potential of esophageal squamous carcinoma through miR-26b-5p/ITGB1 axis

Sep 21, 2026

Long non-coding RNAs, including SNHG6, are explored for their role in esophageal squamous cell carcinoma (ESCC). SNHG6 expression is reported as upregulated in ESCC tissues, and higher SNHG6 levels correlate with advanced TNM stage and worse clinical outcomes. Knockdown experiments in vitro and in vivo suppress ESCC proliferation, invasion, and metastasis. Mechanistically, SNHG6 is validated as a ceRNA that sponges miR-26b-5p to regulate ITGB1 and to modulate EMT via rescue analyses, linking the SNHG6–miR-26b-5p–ITGB1 axis to metastatic progression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN SNHG6 facilitates the epithelialmesenchymal transition and metastatic potential of esophageal squamous carcinoma through miR- 26b-5p/ ITGB1 axis Jiali Wang1, Jiaxin Si1, Ziyuan Zhao1, Changlin Gao1, Tianxu Liu1, Yunlong Jia1 & Lihua Liu1,2􀀍 Long non-coding RNAs (lncRNAs), such as SNHG6, have been identified as crucial regulators in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Although the role of SNHG6 in ESCC is not completely understood, our findings demonstrated that SNHG6 expression is upregulated in ESCC tissues compared to adjacent normal tissues. Furthermore, elevated levels of SNHG6 are significantly correlated with higher TNM stage and poorer clinical prognosis in ESCC patients. Functionally, both in vivo and in vitro experiments have shown that knocking down SNHG6 inhibits proliferation, invasion, and metastasis. Luciferase reporter assays and Ago2-RIP assay confirm that SNHG6 functions as a competing endogenous RNA (ceRNA) by sponging miR-26b-5p to modulate ITGB1 expression in ESCC. Given that ITGB1 is instrumental in EMT and metastasis, we assessed the expression of EMT-related proteins. The findings suggest that miR-26b-5p and reduced ITGB1 expression can reverse the EMT induced by lncRNA SHNG6, as demonstrated through rescue analysis. Overall, this study aims to elucidate the molecular mechanisms through which SNHG6 promotes EMT and metastasis in ESCC, providing a novel theoretical foundation for understanding ESCC progression and identifying new targets for improving outcomes in metastatic ESCC. Keywords Esophageal squamous carcinoma, SNHG6, MiR-26b-5p/ITGB1, EMT Esophageal squamous carcinoma (ESCC) is a malignancy with an increasingly high prevalence and is a leading cause of cancer-related deaths worldwide1. Despite significant advances in oncological treatments, including combined multi-disciplinary management, the prognosis for ESCC remains poor with a 5-year overall survival rate of about 15%2. Distant metastasis constitutes the primary obstacle to improving therapeutic outcomes. Therefore, developing more effective strategies through a better understanding of the molecular mechanisms underlying metastasis is crucial. Long non-coding RNAs (lncRNAs) are identified as a class of RNA molecules exceeding 200 nucleotides in length with limited protein-coding capacity3. Numerous studies have demonstrated that lncRNAs are involved in wide array of biological functions, including cell migration, cellular phenotypic transformation, drug resistance, and disease pathogenesis4–6. Recent research has identified many lncRNAs acting as oncogenesor tumor suppressor genes in ESCC. For instance, lncRNA-DGCR5 acts as a potential oncogene in ESCC, significantly enhancing ESCC cell progression by inhibits TTP’s anti-inflammatory activity7. Additionally, Cui Y. et al. showed that m6A-mediated epigenetic modification of LncRNA contributes to the tumorigenesis in ESCC and LINC00022, specific target of m6A, serves as a potential biomarker for this malignancy8. LncRNAs participate in nearly every regulatory step of gene expression, including chromatin remodeling, transcriptional control, splicing regulation, mRNA stability, mRNA translation, microRNA processing, DNA damage, and drug resistance9–14. Recently, lncRNAs have been recognized for their role in miRNA binding site sponging, leading to the concept of competing endogenous RNA (ceRNA)15. Specifically, many lncRNAs have been shown to indirectly regulate gene expression by functioning as ceRNA in the progression of ESCC. 1Department of Tumor Immunotherapy, Hebei Medical University Fourth Affiliated Hospital, Hebei Provincial Tumor Hospital, Shijiazhuang 050035, China. 2China International Cooperation Laboratory of Stem Cell Research, Hebei Medical University, Shijiazhuang 050011, China. 􀀍 email: [cdlihualiu@hebmu.edu.cn](cdlihualiu@hebmu.edu.cn)

FAQs

How does SNHG6 expression relate to ESCC clinical outcomes?

SNHG6 is upregulated in ESCC tissues, and elevated SNHG6 associates with higher TNM stage and poorer prognosis.

What functional effects does SNHG6 knockdown have on ESCC cells?

Knocking down SNHG6 inhibits proliferation, invasion, and metastasis in both in vitro and in vivo experiments.

What molecular mechanism links SNHG6 to EMT and metastasis?

SNHG6 acts as a ceRNA that sponges miR-26b-5p to modulate ITGB1 expression; reduced ITGB1 can reverse EMT induced by SNHG6, supported by rescue analyses.

Sep 21, 2026

Uploaded by River Wang