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SLCO4A1-AS1 Facilitates the Malignant Phenotype via miR-149-5p/STAT3 Axis in Gastric Cancer Cells
Qing Li1, Dachuan Zhang1, Hui Wang1
1Department of Pathology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Abstract:
Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1), a newly discovered lncRNA, may exert effects in tumors. Since its role in gastric cancer remains obscure, we sought to explore the mechanism of SLCO4A1-AS1 in gastric cancer. The relationship among SLCO4A1-AS1, miR-149-5p, and STAT3 was detected by bioinformatics, dual luciferase analysis, and Pearson's test, and the expressions of these genes were determined by quantitative real-time PCR and Western blot. Moreover, CCK-8, flow cytometry, wound healing assay, and Transwell analysis were performed to verify the function of SLCO4A1-AS1 in gastric cancer. Rescue experiments were used to detect the role of miR-149-5p. The expressions of SLCO4A1-AS1 and STAT3 were increased, while the expression of miR-149-5p was suppressed in gastric cancer tissues and cell lines. In addition, STAT3 expression was negatively correlated with miR-149-5p expression but was positively correlated with SLCO4A1-AS1 expression. Overexpression of SLCO4A1-AS1 promoted cell viability, migration, invasion, and STAT3 expression but suppressed apoptosis, while knockdown of SLCO4A1-AS1 had the opposite effect. SLCO4A1-AS1 bound to miR-149-5p and targeted STAT3. Moreover, miR-149-5p mimic inhibited the malignant development of gastric cancer cells and obviously reversed the function of SLCO4A1-AS1 overexpression. Our research reveals that abnormally increased SLCO4A1-AS1 expression may be an important molecular mechanism in the development of gastric cancer.
Insights
Newly discovered long non-coding RNA, SLCO4A1-AS1, promotes gastric cancer progression by targeting miR-149-5p and upregulating STAT3. This finding reveals a novel molecular mechanism in gastric cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer remains a significant global health challenge.
- The role of long non-coding RNAs (lncRNAs) in tumorigenesis is increasingly recognized.
- The specific function of Solute carrier organic anion transporter family member 4A1 (SLCO4A1-AS1) in gastric cancer is largely unknown.
Purpose of the Study:
- To elucidate the underlying molecular mechanism of SLCO4A1-AS1 in gastric cancer.
- To investigate the interplay between SLCO4A1-AS1, miR-149-5p, and STAT3 in gastric cancer.
- To assess the functional role of SLCO4A1-AS1 in gastric cancer cell behavior.
Main Methods:
- Bioinformatics analysis, dual luciferase reporter assays, and Pearson correlation analysis to determine gene interactions.
- Quantitative real-time PCR and Western blot to measure gene and protein expression levels.
- Cell Counting Kit-8 (CCK-8), flow cytometry, wound healing, and Transwell assays to evaluate cellular functions; rescue experiments were performed.
Main Results:
- SLCO4A1-AS1 and STAT3 expression were upregulated, while miR-149-5p was downregulated in gastric cancer tissues and cell lines.
- SLCO4A1-AS1 positively correlated with STAT3 expression and negatively correlated with miR-149-5p expression.
- Overexpression of SLCO4A1-AS1 enhanced cell viability, migration, and invasion, suppressed apoptosis, and increased STAT3 expression. Conversely, knockdown of SLCO4A1-AS1 showed opposite effects.
- SLCO4A1-AS1 directly targets miR-149-5p, which in turn targets STAT3. Overexpression of miR-149-5p reversed the oncogenic effects of SLCO4A1-AS1.
Conclusions:
- Abnormally elevated SLCO4A1-AS1 expression is implicated in the development of gastric cancer.
- The SLCO4A1-AS1/miR-149-5p/STAT3 axis represents a critical molecular mechanism driving gastric cancer progression.
- SLCO4A1-AS1 may serve as a potential therapeutic target for gastric cancer treatment.
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