Current medicinal chemistry · 2026
Knockdown of circFGFR2 inhibits prostate cancer cell metastasis and proliferation by targeting miR-221-5p/ SMUG1 pathway....
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Li Wei, Fan Jiqing, Deng Ling, Xu Shi, Peng Naixiong
Аннотация
OBJECTIVE: The objective of this study is to elucidate the contribution of circFGFR2 in Prostate Cancer (PC) cells and to identify the associated molecular regulatory mechanisms.
METHODS: This study evaluated circFGFR2 levels in PC cell lines and tissues by qRTPCR. Furthermore, the impact of circFGFR2 knockdown on the invasion, migration, proliferation, and viability of PC cells was explored using CCK-8, colony formation, Transwell, and wound-healing assays. Moreover, bioinformatics analysis and luciferase reporter assays were used to analyze the binding interactions between circFGFR2, miR-221-5p, and SMUG1. In vitro functional assays further confirmed that circFGFR2 modulates the proliferation and migration of the PC cells via the miR-221-5p/SMUG1 signaling pathway. Lastly, a xenograft mouse model was established to assess the impact of circFGFR2 knockdown on in vivo tumor growth.
RESULTS: The data showed that circFGFR2 was significantly upregulated in PC tissues. Furthermore, in vitro and in vivo analyses revealed that circFGFR2 silencing markedly reduced the invasion, proliferation, migration, and colony formation of PC cells. Mechanistic studies demonstrated that circFGFR2 functions as a competitive endogenous RNA (ceRNA) to sequester miR-221-5p, which subsequently downregulates SMUG1 expression. Rescue experiments confirmed that circFGFR2 modulates PC cell migration and proliferation via the miR-221-5p/SMUG1 pathway. These data suggest that circFGFR2 functions as a tumor-promoting circRNA by sponging miR-221-5p, thereby derepressing SMUG1. Therefore, circFGFR2 should be evaluated as a clinical biomarker for risk stratification and prognosis. Moreover, targeting circFGFR2 or restoring the miR-221-5p/SMUG1 balance are effective strategies for inhibiting PC cells' growth and dissemination, extending the circRNA-based framework for precision therapeutic intervention.
DISCUSSION: These data identify circFGFR2 as a tumor-promoting circRNA that acts as a sponge for miR-221-5p, thereby derepressing SMUG1. Moreover, targeting circFGFR2 or restoring the miR-221-5p/SMUG1 balance represents a tractable axis to curb PCa, and are effective strategy for inhibiting PC cells' growth and dissemination, offering an effective strategy that extends the circRNA-based framework for precision therapeutic intervention.
CONCLUSION: This study indicates that circFGFR2 influences PC cell proliferation and migration via the miR-221-5p/SMUG1 signaling axis. Therefore, circFGFR2 may serve as a potential therapeutic target and a unique molecular biomarker for PC.
METHODS: This study evaluated circFGFR2 levels in PC cell lines and tissues by qRTPCR. Furthermore, the impact of circFGFR2 knockdown on the invasion, migration, proliferation, and viability of PC cells was explored using CCK-8, colony formation, Transwell, and wound-healing assays. Moreover, bioinformatics analysis and luciferase reporter assays were used to analyze the binding interactions between circFGFR2, miR-221-5p, and SMUG1. In vitro functional assays further confirmed that circFGFR2 modulates the proliferation and migration of the PC cells via the miR-221-5p/SMUG1 signaling pathway. Lastly, a xenograft mouse model was established to assess the impact of circFGFR2 knockdown on in vivo tumor growth.
RESULTS: The data showed that circFGFR2 was significantly upregulated in PC tissues. Furthermore, in vitro and in vivo analyses revealed that circFGFR2 silencing markedly reduced the invasion, proliferation, migration, and colony formation of PC cells. Mechanistic studies demonstrated that circFGFR2 functions as a competitive endogenous RNA (ceRNA) to sequester miR-221-5p, which subsequently downregulates SMUG1 expression. Rescue experiments confirmed that circFGFR2 modulates PC cell migration and proliferation via the miR-221-5p/SMUG1 pathway. These data suggest that circFGFR2 functions as a tumor-promoting circRNA by sponging miR-221-5p, thereby derepressing SMUG1. Therefore, circFGFR2 should be evaluated as a clinical biomarker for risk stratification and prognosis. Moreover, targeting circFGFR2 or restoring the miR-221-5p/SMUG1 balance are effective strategies for inhibiting PC cells' growth and dissemination, extending the circRNA-based framework for precision therapeutic intervention.
DISCUSSION: These data identify circFGFR2 as a tumor-promoting circRNA that acts as a sponge for miR-221-5p, thereby derepressing SMUG1. Moreover, targeting circFGFR2 or restoring the miR-221-5p/SMUG1 balance represents a tractable axis to curb PCa, and are effective strategy for inhibiting PC cells' growth and dissemination, offering an effective strategy that extends the circRNA-based framework for precision therapeutic intervention.
CONCLUSION: This study indicates that circFGFR2 influences PC cell proliferation and migration via the miR-221-5p/SMUG1 signaling axis. Therefore, circFGFR2 may serve as a potential therapeutic target and a unique molecular biomarker for PC.