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HOTAIR Induces the Downregulation of miR-200 Family Members in Gastric Cancer Cell Lines
Fatemeh Bossaghzadeh1, Mohammadreza Hajjari2, Abdolkarim Sheikhi3
1Department of Biology, Science and research Branch, Islamic Azad University, Tehran, Iran.
Background:
Gastric cancer (GC) is the fourth most common human malignancy and the second reason for cancer morbidity worldwide. Long noncoding RNA (LncRNA) HOX transcript antisense RNA (HOTAIR) has recently emerged as a promoter of metastasis in various cancer types, including GC, through the epithelial‑mesenchymal transition (EMT) process. However, the exact mechanism of HOTAIR in promoting EMT is unknown. Aberrant expression of the miR-200 family has been linked to the occurrence and development of various types of malignant tumors. This study investigates the correlation between the HOTAIR and miR-200 family gene expression patterns in GC cell lines. We investigated the miR-200 and HOTAIR due to their common molecular features in the EMT process.
Methods:
AGS and MKN45 cell lines were transfected with si-HOTAIR, along with a negative control. The effect of HOTAIR knockdown was also analyzed on cell viability and also on the expression of miR-200 family members, including miR-200a, -200b, and -200c, in cell lines using qRT-PCR. Statistical analysis was performed to find the potential correlation between the expression level of HOTAIR and miRs.
Results:
Our results showed significant increased miR-200 family expression level in transfected AGS and MKN45 GC cells (fold changes > 2; p < 0.001). Moreover, a negative correlation was observed between HOTAIR and miR-200 expression levels in GC cell lines (p < 0.05).
Conclusion:
Our findings showed a significant association between miR-200 family and HOTAIR expression levels in GC cell lines. Taken together, the HOTAIR-miR-200 axis seems to play a vital role in human GC, suggesting a potential therapeutic target in future GC treatment.
Insights
Long noncoding RNA HOTAIR promotes gastric cancer metastasis by suppressing the miR-200 family. This HOTAIR-miR-200 axis represents a potential therapeutic target for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) is a leading cause of cancer mortality globally.
- Long noncoding RNA HOTAIR is implicated in promoting metastasis via epithelial-mesenchymal transition (EMT) in various cancers, including GC.
- The precise mechanism of HOTAIR in driving EMT and the role of the miR-200 family in GC remain incompletely understood.
Purpose of the Study:
- To investigate the correlation between HOTAIR and miR-200 family gene expression in gastric cancer cell lines.
- To elucidate the role of the HOTAIR-miR-200 axis in the context of gastric cancer progression and EMT.
Main Methods:
- Gastric cancer cell lines (AGS and MKN45) were transfected with si-HOTAIR to achieve HOTAIR knockdown.
- Quantitative reverse transcription PCR (qRT-PCR) was employed to assess cell viability and the expression levels of miR-200 family members (miR-200a, -200b, -200c).
- Statistical analyses were performed to determine the correlation between HOTAIR and miR-200 expression.
Main Results:
- HOTAIR knockdown led to a significant increase (>2-fold change; p < 0.001) in miR-200 family expression in GC cell lines.
- A significant negative correlation (p < 0.05) was observed between HOTAIR and miR-200 expression levels in the studied GC cell lines.
Conclusions:
- A significant association exists between the miR-200 family and HOTAIR expression in gastric cancer.
- The HOTAIR-miR-200 axis plays a crucial role in human gastric cancer, indicating its potential as a therapeutic target for future GC treatments.
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