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Downregulated Circular RNA hsa_circ_0000291 Suppresses Migration And Proliferation Of Gastric Cancer Via Targeting
Chuanwu Cao1, Shilong Han1, Yifeng Yuan1
1Department of Interventional and Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai 200072, People's Republic of China.
Background:
Circular RNAs are implicated in a variety of cancers. This investigation found that hsa_circ_0000291 expression was upregulated in gastric cancer (GC) cell lines, yet its role in GC has not yet been reported.
Objective:
To explore the effects of hsa_circ_0000291 on GC cell proliferation and invasion.
Materials And Methods:
In the current research, we used the gastric cancer cell lines MGC803 and MKN-28 to study hsa_circ_0000291 function. The relationship between hsa_circ_0000291, miR-183 and ITGB1 was analyzed by firefly luciferase analysis and Western blots, and qRT-PCR approaches were used for protein and gene expression analysis, respectively. Tumor growth and metastasis were determined in nude mice xenografts using MKN-28 cells, with or without hsa_circ_000r0291 downregulation.
Results:
Our data showed that hsa_circ_0000291 was upregulated in GC cell lines, whereas hsa_circ_0000291 silencing suppressed cell metastasis and proliferation in in vivo and in vitro studies. Our results showed that the downregulation of hsa_circ_0000291 suppressed integrin beta 1 (ITGB1) expression via miR-183 "sponging," which was validated by rescue experiments using the luciferase reporter assay. Our observations suggested that hsa_circ_0000291 silencing suppressed the aggressive, metastatic GC phenotype.
Conclusion:
Taken together, hsa_circ_0000291 knockdown inhibited GC cell metastasis and growth by regulating the miR-183/ITGB1 axis. Importantly, this approach could provide a therapy target and potential biomarker for the diagnosis and treatment of GC.
Insights
Circular RNAs like hsa_circ_0000291 are upregulated in gastric cancer. Silencing hsa_circ_0000291 inhibits cancer growth and metastasis by regulating the miR-183/ITGB1 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
- hsa_circ_0000291 expression is elevated in gastric cancer (GC) cell lines.
- The specific function of hsa_circ_0000291 in GC remains largely uncharacterized.
Purpose of the Study:
- To investigate the functional impact of hsa_circ_0000291 on gastric cancer cell proliferation and invasion.
- To elucidate the molecular mechanism underlying hsa_circ_0000291's role in GC progression.
Main Methods:
- Gastric cancer cell lines (MGC803, MKN-28) were utilized to study hsa_circ_0000291.
- Gene and protein expression analyzed via qRT-PCR and Western blots.
- MiR-183 sponging activity and ITGB1 regulation assessed using luciferase reporter assays and rescue experiments.
- In vivo tumor growth and metastasis evaluated in nude mouse xenograft models.
Main Results:
- hsa_circ_0000291 expression was significantly upregulated in GC cell lines.
- Silencing hsa_circ_0000291 suppressed both in vitro and in vivo gastric cancer cell proliferation and metastasis.
- Downregulation of hsa_circ_0000291 led to reduced integrin beta 1 (ITGB1) expression through miR-183 sponging.
- Rescue experiments confirmed the interaction between hsa_circ_0000291, miR-183, and ITGB1.
Conclusions:
- Knockdown of hsa_circ_0000291 effectively inhibited gastric cancer cell growth and metastasis.
- The observed effects are mediated by the regulation of the miR-183/ITGB1 axis.
- hsa_circ_0000291 presents a potential therapeutic target and diagnostic biomarker for gastric cancer.
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