miR-215-5p Plays a Key Role in Suppressing Vascular Invasion and Recurrence in Hepatocellular Carcinoma by Blocking Vasculogenic Mimicry.

BACKGROUND: This research explores the significance of miR-215-5p and vasculogenic mimicry (VM) in forecasting the prognosis for hepatocellular carcinoma (HCC). METHODS: We analyzed HCC-associated miRNA expression profiles using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Samples included tissue and blood from 80 early-stage HCC patients and serum from 120 healthy individuals. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was employed to measure miR-215-5p and zinc finger E-box binding homeobox 2 (ZEB2) gene expressions. Hematoxylin and eosin (H&E) and CD34/Periodic Acid-Schiff (PAS) double staining assessed VM presence in HCC tissue sections. Bioinformatics tools predicted interactions between miR-215-5p and ZEB2, confirmed through luciferase reporter assays. We also examined the impact of miR-215-5p or ZEB2 overexpression on HCC cell invasion, migration, and VM formation using scratch, Transwell invasion assays, and Matrigel 3D cultures. RESULTS: Bioinformatics analysis indicated that miR-215-5p was under-expressed in HCC, particularly in cases with vascular invasion, which correlated with worse patient outcomes. In contrast, ZEB2, targeted by miR-215-5p, was overexpressed in HCC. RT-qPCR validated these expression patterns in HCC tissues. Among the HCC patients, 38 were VM positive and 42 VM negative. Logistic regression highlighted a negative correlation between miR-215-5p levels and VM positivity in HCC tissues and a positive correlation for ZEB2 with VM positivity and tumor vascular invasion. Lower miR-215-5p levels were linked to increased HCC recurrence and metastasis. Both bioinformatics analysis and luciferase assays demonstrated a direct interaction between miR-215-5p and ZEB2. Enhancing miR-215-5p levels reduced ZEB2 expression, consequently diminishing invasion, migration, and VM formation of the HCC cells in vitro. CONCLUSIONS: miR-215-5p expression inversely correlates with VM occurrence in HCC tissues, while ZEB2 expression shows a direct correlation. By targeting ZEB2, miR-215-5p may hinder VM in HCC tissues, helping to prevent vascular invasion and HCC recurrence. Thus, miR-215-5p emerges as a vital prognostic indicator for predicting vascular invasion and recurrence in HCC.

Overexpression of the long non-coding RNA, linc-UBC1, is associated with poor prognosis and facilitates cell proliferation, migration, and invasion in colorectal cancer.

Long non-coding RNAs (lncRNAs) serve comprehensive roles in various diseases, including cancer. lncRNA upregulated in bladder cancer 1 (linc-UBC1) is a notable biomarker of prognosis in certain cancer types; however, its involvement in the progression of colorectal cancer (CRC) remains unknown. The present study aimed to investigate the expression of linc-UBC1 in patients with CRC and to investigate its effect on CRC cells. The expression levels of linc-UBC1 were estimated by reverse transcription-quantitative polymerase chain reaction in clinical CRC specimens and matched adjacent non-tumor mucosa from 96 cases of CRC, as well as in a number of CRC cell lines. In addition, the biological roles of linc-UBC1 were examined using a cell counting kit-8 assay, flow cytometry, and migration and invasion assays following the downregulation of linc-UBC1 by small interfering RNA. The results revealed that linc-UBC1 was significantly overexpressed in CRC tissues and the majority of CRC cell lines compared with the matched non-tumor mucosa and normal intestinal epithelial cells. Furthermore, high expression levels of linc-UBC1 were significantly associated with large tumor size, greater tumor depth, lymph node metastasis, and advanced tumor-node-metastasis stages. Patients with abnormal expression of linc-UBC1 had poorer overall survival times according to Kaplan-Meier analyses. Furthermore, multivariate Cox regression analysis indicated that linc-UBC1 was a significant independent prognostic factor. The results also revealed that reducing the expression of linc-UBC1 led to the inhibition of migration, invasion, and proliferation of CRC cells in vitro. Taken together, the results of the present study suggest that overexpression of linc-UBC1 promotes proliferation and metastasis in CRC, and may be considered as a novel diagnostic marker of CRC.