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Sinomenine regulates circTRPM7-related pathway to inhibit gastric cancer cell growth and metastasis
Jingwei Yan1, Jingqing Yang2, Huifen Shen1
1Department of Traditional Chinese Medicine, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China.
Abstract:
Sinomenine has been found to have antitumor effects in a variety of cancers, including gastric cancer. Circular RNA (circRNA) is an important regulator of gastric cancer progression. However, it is not known whether Sinomenine mediates gastric cancer processes by regulating circRNA-related pathways. Quantitative real-time PCR was used to measure the expression of circTRPM7, microRNA-145-5p (miR-145-5p), and pre-B-cell leukemia homeobox 3 (PBX3). MTT assay, colony formation assay, EdU assay, transwell assay, wound-healing assay, and flow cytometry were used to detect cell proliferation, migration, invasion, and apoptosis. The expression of related proteins was detected by Western blot. Mechanically, the interaction of miR-145-5p with circTRPM7/PBX3 was validated by dual-luciferase reporter assay and RIP assay. Our study showed that circTRPM7 expression was reduced in Sinomenine-treated gastric cancer cells. Moreover, overexpression of circTRPM7 upregulated the growth and metastasis of Sinomenine-treated gastric cancer cells. CircTRPM7 could sponge miR-145-5p, and miR-145-5p reversed the effect of circTRPM7 on the growth and metastasis of Sinomenine-treated gastric cancer cells. PBX3 was the target of miR-145-5p, and knockdown of PBX3 could restore the in-miR-145-5p promotion effect on the malignant behavior of Sinomenine-treated gastric cancer cells. To sum up, our data indicated that Sinomenine played an antitumor role in gastric cancer cells via circTRPM7/miR-145-5p/PBX3 axis.
Insights
Sinomenine exhibits antitumor properties in gastric cancer by regulating the circTRPM7/microRNA-145-5p/PBX3 pathway, inhibiting cancer cell growth and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sinomenine demonstrates antitumor potential in various cancers, including gastric cancer.
- Circular RNAs (circRNAs) are implicated in gastric cancer progression, but their interaction with Sinomenine is unclear.
Purpose of the Study:
- To investigate whether Sinomenine exerts its antitumor effects in gastric cancer by modulating circRNA pathways.
- To elucidate the specific molecular mechanisms involving circTRPM7, microRNA-145-5p, and PBX3.
Main Methods:
- Quantitative real-time PCR for gene expression analysis.
- Cellular assays (MTT, colony formation, EdU, Transwell, wound-healing, flow cytometry) for proliferation, migration, invasion, and apoptosis.
- Western blot for protein analysis and dual-luciferase/RIP assays for molecular interactions.
Main Results:
- Sinomenine treatment reduced circTRPM7 expression in gastric cancer cells.
- Overexpression of circTRPM7 promoted growth and metastasis, while circTRPM7 sponged miR-145-5p, which reversed these effects.
- miR-145-5p targeted PBX3, and PBX3 knockdown counteracted miR-145-5p's tumor-suppressive actions.
Conclusions:
- Sinomenine exerts an antitumor role in gastric cancer.
- This effect is mediated through the circTRPM7/miR-145-5p/PBX3 axis, highlighting a novel therapeutic pathway.
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