Abstract
The interaction of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs has been implicated in various types of cancers, including esophageal cancer (EC). The current study aimed to investigate the role of AGAP2-AS1/miR-195-5p/Fos-like antigen-1 (FOSL1) in EC progression. The expression of AGAP2-AS1, miR-195-5p, and FOSL1 in tumor tissues isolated from EC patients and EC cell lines was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which illustrated that AGAP2-AS1 and FOSL1 were increased while miR-195-5p was reduced in EC. Next, the ectopic expression, knockdown, and reporter assay experiments were all employed to elucidate the mechanism of AGAP2-AS1/miR-195-5p/FOSL1 in the processes of EC cell proliferation, cell cycle, apoptosis, invasion, and migration as well as tumor growth. Knockdown of AGAP2-AS1 or overexpression of miR-195-5p reduced EC cell proliferation, migration, and invasion, blocked cell cycle entry, and elevated apoptosis. FOSL1 was found to be specifically targeted by miR-195-5p. AGAP2-AS1 was observed to upregulate FOSL1 by binding to miR-195-5p. Silencing of AGAP2-AS1 was observed to restrain the development of EC both in vitro and in vivo through upregulating miR-195-5p and downregulating FOSL1. Taken together, AGAP2-AS1 knockdown exercises suppressive effects on the development of EC through miR-195-5p-dependent downregulation of FOSL1. Therefore, targeting AGAP2-AS1 could be a future direction to develop a novel molecule-targeted therapeutic strategy for EC.
Highlights
As one of the most deadly diseases worldwide, esophageal cancer (EC) is a malignancy characterized by rapid progression and poor patient prognosis.[1]
The expression heatmap of the top 10 differentially expressed miRNAs screened from gene expression datasets (GEO): GSE43732 is depicted in Figure 1A, among which two miRNAs were found to be upregulated, and the others were downregulated in EC
MiR-195-5p was identified to be poorly expressed in EC based on another dataset, GEO: GSE97049 (Figure 1B)
Summary
As one of the most deadly diseases worldwide, esophageal cancer (EC) is a malignancy characterized by rapid progression and poor patient prognosis.[1]. Tremendous strides have been made in the treatment of EC, such as chemotherapy and surgical resection, patients diagnosed with EC still have poor prognosis, with a relatively low 5-year survival of only about 10%.3,4 Long non-coding RNAs (lncRNAs), longer than 200 nt, have been highlighted to be essential for the tumorigenesis and progression of EC.[5,6] High expression of AGAP2-AS1 has been identified in gastric cancer and non-small-cell lung cancer, suggesting that knockdown of AGAP2-AS1 leads to a decrease in cell proliferation and migration, along with the repression of invasion and tumorigenesis.[7,8] it remains unknown as to whether AGAP2-AS1 influences cancer progression in EC
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