Circ0043898 acts as a tumor inhibitor and performs regulatory effect on the inhibition of esophageal carcinoma

Abstract

Objective: The study aimed to investigate candidate circular RNAs (circRNAs) in regulating the pathogenic process of esophageal carcinoma. Methods: Specimens were collected from the patients with esophageal carcinoma. Total RNA was purified and treated with RNase R followed by RNA-seq in the purpose of screening the circRNAs in significant differentially expression. The expression level of the screened circRNAs were further validated using RT-PCR. The circular structure of the circRNA was validated with divergent and convergent primers. Overexpression vector was prepared in the purpose of raising the expression level of circ0043898 in the ECA-109 and Kyse-520 cells. The cell colony assay and MTS assay were conducted to determine the capacity of cell proliferation. Chamber assays were applied to determine the capacity of cell migration and invasion while flowcytometry was applied to determine the cell cycle and cell apoptosis. In vivo animal assay was conducted by injecting the cells to the chest of the mice. RNA-seq was performed followed by GO and KEGG study to further verify the regulation mechanism of circ0043898. Results: circ0043898 was validated that down-regulated expressed in the specimens from the patients with esophageal carcinoma. The cell assays proved that overexpression of circ0043898 can obviously inhibit the cell proliferation, cell migration and invasion and induce cell apoptosis and death in the cancerous cells. The in vivo animal study also suggested that the circ0043898 performed inhibitory functions on oncogenesis. The RNA-seq presented the potential regulation mechanism of circ0043898. Histone H3 and BMI1 were presented significantly differential expression in both ECA-109 and Kyse-520 cells, indicating they might be the targets of circ0043898. Conclusion: circ0043898 is presented as tumor inhibitor and could be a candidate biomarker in the therapeutic target and diagnosis of esophageal carcinoma.

RETRACTED ARTICLE: A regulatory circuit of circ-MTO1/miR-17/QKI-5 inhibits the proliferation of lung adenocarcinoma

“…Numerous studies have shown that circRNA is more suitable as a tumor biomarker than linear and long noncoding RNA due to its long half-life and stability. 22 For example, circ-104075, 23 circ-0043898, 24 circ-ANKS1B, 25 and circ-PVT1 26 were identified as biomarkers for hepatocellular carcinoma, esophageal carcinoma, breast cancer, and gastric cancer, respectively. Similarly, we found that LUAD patients with low circ-MTO1 expression had a shorter overall (P < 0.001) or progression-free survival (P < 0.001) time than those with high circ-MTO1 expression, indicating that endogenous circ-MTO1 is a promising prognostic predictor for LUAD patients.…”

Tumor‐suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets

“…In addition, circ004389 may be a target of histone H3 and BMI1 proto‐oncogene in esophageal cancer. It inhibits cell proliferation, migration, and invasion and induces cell death …”

CircRNAs: a new target for the diagnosis and treatment of digestive system neoplasms

“…In addition, the expression of circ-Foxo3 is low in ESCC, and the circ-Foxo3/miR-23a/PTEN pathway is the key pathway that inhibits the progression of ESCC 49 . Some circRNAs, such as circ0043898 and circ-SMAD7, show low expression in ESCC, while upregulation of their expression inhibits biological functions in esophageal cancer cells 50 , 51 .…”