Long noncoding RNA SNHG12 induces proliferation, migration, epithelial–mesenchymal transition, and stemness of esophageal squamous cell carcinoma cells via post‐transcriptional regulation of BMI1 and CTNNB1

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors around the world. Numerous studies have revealed the function of long noncoding RNAs (lncRNAs) in cancers, including ESCC. In this study, lncRNA small nucleolar RNA host gene 12 (SNHG12), mainly distributed in ESCC cell cytoplasm, was overexpressed in ESCC specimens and CD133+ cells. In CD133‐ ESCC cells, SNHG12 overexpression promoted cell proliferation, migration, epithelial–mesenchymal transition (EMT), and stemness and SNHG12 silencing led to opposite results. Furthermore, SNHG12 sequestered miR‐6835‐3p and induced the proto‐oncogene, polycomb ring finger (BMI1). SNHG12 also enhanced the stability of CTNNB1, the mRNA encoding β‐catenin, via recruiting insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) in ESCC. Rescue assays indicated that CTNNB1 and BMI1 were targets for SNHG12 to regulate ESCC cell proliferation, migration, EMT, and stemness. Furthermore, SOX4 (sex‐determining region Y‐box 4) bound with the SNHG12 promoter to transcriptionally activate SNHG12 in ESCC. Finally, in vivo data showed SNHG12 knockdown retarded tumorigenesis and metastasis in ESCC. In summary, SNHG12 induces proliferation, migration, EMT, and stemness of ESCC cells via post‐transcriptional regulation of BMI1 and CTNNB1, indicating that targeting SNHG12 might be a novel target for ESCC treatment.

Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective

“…ARK5/NUAK1 and HOXA10, as the regulatory factors in EMT cascade loop, were remarkably upregulated, when compared with adjacent normal tissues, thus enhancing invasiveness of ovarian cancer [ 15 ]. In the main signaling pathways closely related to EMT, BIRC5, CTNNB1 and relevant other proteins could also enhance the migration and proliferation of ovarian cancer cells with the expression of EMT markers [ 16 , 17 ]. Meanwhile, PARP-1, also as a core EMT regulator, could play an important role in OSC progression [ 18 , 19 ].…”

YY1-modulated long non-coding RNA SNHG12 promotes gastric cancer metastasis by activating the miR-218-5p/YWHAZ axis

“…The Wnt/β-catenin signaling pathway is well-established to regulate cancer cell EMT and invasion. SNHG12 recruits IGF2BP2 to enhance the stability of CTNNB1, the gene encoding β-catenin [25]. The YWHAZ-encoded protein (14-3-3ζ) is capable of activating the β-catenin pathway by inducing the accumulation of β-catenin in the cytosol and nucleus [26,27].…”

Small nucleolar RNA host genes promoting epithelial–mesenchymal transition lead cancer progression and metastasis

“…Noteworthy, SNHGs have an important role in esophageal cancer as well. For example, SNHG1, 12, 16, and 20 are responsible for cancer progression in part through the Notch, BMI1‐CTNNB1, ZEB1, ATM‐JAK‐PD‐L1 signaling pathways, respectively 78,93–95 …”