LncRNA SNHG3 Facilitates the Malignant Phenotype of Cholangiocarcinoma Cells via the miR-3173–5p/ERG Axis

• Published in: Journal of gastrointestinal surgery 2022-04, Vol.26 (4), p.802-812
• Main Authors: Sun, Zeng-Peng, Tan, Zhi-Guo, Peng, Chuang, Yi, Wei-Min
• Format: Article
• Language: English
• Subjects: Apoptosis; Bile Duct Neoplasms - pathology; Bile Ducts, Intrahepatic - pathology; Binding sites; Cancer; Cell culture; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Cholangiocarcinoma - pathology; Flow cytometry; Gastroenterology; Gastrointestinal surgery; Gene expression; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Humans; Leukemia; Medicine; Medicine & Public Health; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Original Article; Phenotype; Plasmids; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Surgery; Transcriptional Regulator ERG - genetics; Transcriptional Regulator ERG - metabolism
• ISSN: 1091-255X; 1873-4626
• DOI: 10.1007/s11605-021-05160-5

Background Long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) is an oncogenic lncRNA that has been reported in many cancers, but the role of SNHG3 in cholangiocarcinoma (CCA) remains largely unknown. Bioinformatic analysis revealed a regulatory relationship among SNHG3, miR-3173–5p, and ERG. miR-3173–5p is a tumour suppressive miRNA, while ERG is an oncogene. In the present study, we focused on the regulatory effects and molecular mechanisms of SNHG3 in CCA. Method The expression of SNHG3 and miR-3173–5p was evaluated using qRT–PCR analysis. Knockdown of SNHG3 was achieved by shRNA. Cell viability was assessed by MTT assay. Migration and invasion were determined by Transwell assay. Flow cytometry was used to assess cell apoptosis. Western blots were applied to quantify protein levels. Furthermore, using RNA pulldown and dual luciferase assays, the interactions between SNHG3 and miR-3173–5p and between miR-3173–5p and ERG in CCA cells were validated. Results SNHG3 was significantly upregulated in CCA cells compared with normal human intrahepatic biliary epithelial cells. Knockdown of SNHG3 inhibited the proliferation and migration of CCA cells . Mechanistically, SNHG3-sponged miR-3173–5p, thus releasing the repression of ERG by miR-3173–5p. Rescue experiments showed that the miR-3173–5p/ERG axis mediated the oncogenic effect of SNHG3. Conclusion Taken together, our data suggest that SNHG3 is a pleiotropic oncogenic lncRNA in CCA. Knockdown of SNHG3 expression suppressed malignant phenotypes in CCA cells via the miR-3173–5p/ERG axis.