Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1237
Peer-review started: July 24, 2020
First decision: September 17, 2020
Revised: September 27, 2020
Accepted: October 21, 2020
Article in press: October 21, 2020
Published online: November 15, 2020
Processing time: 110 Days and 18.4 Hours
Long non-coding RNAs (lncRNAs) are a class of non-coding RNAs with a length of more than 200 nucleotides and lack an open reading frame. They mainly regulate RNA transcription and mRNA splicing and play an important role in regulating the stability of RNA in the cytoplasm and the activity of microRNAs. More and more studies have shown that abnormally expressed lncRNAs are involved in all aspects of tumor occurrence and development, and are closely related to tumor proliferation, apoptosis, invasion, metastasis, drug resistance, and poor prognosis. In recent years, more and more studies have found that abnormally expressed lncRNAs are involved in the occurrence and development of gastric cancer (GC), and they are expected to become new biomarkers for the diagnosis and treatment of GC.
GC is one of the most common malignant tumors in the world. The incidence and mortality of GC are in the forefront of all malignant tumors. Although a major breakthrough has been achieved in the study of lncRNAs in the pathogenesis of GC, the specific mechanism of lncRNAs in the occurrence and development of GC has not yet been fully elucidated. Exploring new lncRNAs can help to understand the molecular mechanism of GC more deeply.
The main purpose of this study was to explore the effect of downregulation of HOXD-AS2 on the biological behavior of GC cells SGC-7901 and SNU-1 and the underlying mechanism. Studies have found that the downregulation of HOXD-AS2 can regulate the expression of its neighboring gene HOXD8, and can also activate the PI3K/Akt signaling pathway, thereby promoting the progression of GC cells. The results of this study may provide a new idea for the treatment of GC.
The pcHOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXD-AS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.
In this study, we found that the low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.
These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.
This study combines basic experimental research and bioinformatics results to reach a relatively novel conclusion. To further confirm the results of this study, siRNA and animal experiments may be better.