Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p

Abstract

Increasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.

Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration

“…In our study, we screened HCC genes from GEO and TCGA data and identi ed the di erentially expressed molecule Sort1 from the di erential genes. Previous studies have shown that Sort1 acts as an oncogene that is linked with poor prognosis in gastric [24], prostate [25], and colorectal cancers [26], but there is no relevant study on a similar mechanism in HCC. We veri ed the ability of reduced Sort1 expression in inhibiting HCC proliferation and invasion, with the ndings expected to re ect the potential importance of using Sort1 to assess the prognosis of HCC.…”

Emerging roles of circular RNAs in gastric cancer metastasis and drug resistance

“…CircRNAs have multiple remarkable characteristics which provide tremendous potential for serving as biomarkers and therapeutic targets owing to the covalently closed-loop structure, disease-specific and dynamic expression pattern and high conservation across species [118][119][120][121][122]. For example, according to a study by Liang and colleagues, hsa_circ_0110389 has been identified as a diagnostic/prognostic biomarker and therapeutic target for GC [123]. Similarly, circOSBPL10 might serve as a novel proliferation factor and prognostic marker of the OS and disease-free survival (DFS) of GC patients [124].…”

“…The well-characterized mechanism of circRNAs is to sequester miRNAs to regulate the expressions of targeted genes [11][12][13]. A single circRNA could function as a scaffold for several different miRNAs [123]. Conversely, a miRNA can target multiple circRNAs as well [60,61].…”

hsa_circ_0000285 facilitates thyroid cancer progression by regulating miR‐127‐5p/CDH2

“…Subsequently, bioinformatics analysis disclosed that miR-127-5p was the candidate miRNA containing the predicted binding sites for hsa_circ_0000285 and CDH2. Although multitudinous documents elaborate that miR-127-5p was a suppressive factor in various types of human cancers, such as hepatocellular carcinoma, 40 gastric cancer, 41 and cervical cancer, 42 By and large, we illustrated that hsa_circ_0000285 exerted oncogenic functions in THCA via absorbing miR-127-5p to regulate CDH2 expression, which contributed to comprehensively understanding the pathogenesis of THCA and offered a promising therapeutic strategy for THCA patients.…”