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Hsa_circ_0049396 inhibited oral squamous cell carcinoma progression by regulating the miR-663b/ENDOU axis
Ying Lou1, Liuyang Ren1, Lu Wang1
1Department of Stomatology, Henan Provincial People's Hospital, Zhengzhou 450003, Henan, China.
Background:
Circular RNA (circRNAs) play an important role in oral squamous cell carcinoma (OSCC) progression and has been widely reported. In this study, we aimed to investigate the role of a novel circRNA, circ_0049396, and its underlying mechanism in OSCC.
Methods:
The expression levels of circ_0049396, miR-663b, and theuridylate-specific endoribonuclease (ENDOU) were assessed by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation and migration were evaluated using CCK-8 and Transwell assays, respectively. Western blotting was performed to measure the levels of the apoptosis-associated proteins (Bcl-2 and Bax). The functional role of circ _0049396 was further validated in a xenograft experiment in vivo. The interactions of miR-663b with circ_0049396/ENDOU were verified using the dual luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays.
Results:
The expression of circ_0049396 and ENDOU was downregulated in OSCC tissues and cells, whereas miR-663b was upregulated. Circ_0049396 overexpression weakened OSCC cell proliferation and migration but enhanced their apoptosis. Circ_0049396 overexpression suppresses tumorigenesis in vivo. The circ_0049396/miR-663b/ENDOU regulatory network predicted through bioinformatic analysis was validated using RNA pull-down, luciferase reporter, and RIP experiments. MiR-663b mimic enhanced the migratory and proliferative abilities of OSCC cells, but suppressed apoptosis. Furthermore, circ_0049396 or ENDOU overexpression partially reversed the malignant behavior of miR-663b-overexpressing OSCC cells.
Conclusions:
Our study illustrated that circ_0049396 overexpression inhibited the malignant behavior of OSCC cells by regulating the miR-663b/ENDOU axis. Based on our findings, circ_0049396 can be used as a potential therapeutic agent for OSCC.
Insights
Circular RNA (circRNA) circ_0049396 inhibits oral squamous cell carcinoma (OSCC) progression by regulating the miR-663b/ENDOU axis. Overexpression of circ_0049396 shows potential as a therapeutic strategy for OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer progression.
- Oral squamous cell carcinoma (OSCC) is a significant global health concern.
- Understanding novel circRNAs like circ_0049396 is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the function of circ_0049396 in oral squamous cell carcinoma (OSCC).
- To elucidate the underlying molecular mechanism of circ_0049396 in OSCC progression.
- To evaluate circ_0049396 as a potential therapeutic target for OSCC.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) for gene expression analysis.
- Cellular assays (CCK-8, Transwell) for proliferation and migration.
- Western blotting for apoptosis-related proteins.
- In vivo xenograft models for tumorigenesis assessment.
- Molecular interaction studies (dual luciferase, RNA pull-down, RIP assays).
Main Results:
- circ_0049396 and ENDOU were downregulated, while miR-663b was upregulated in OSCC.
- Overexpression of circ_0049396 suppressed OSCC cell proliferation, migration, and tumorigenesis, while enhancing apoptosis.
- The circ_0049396/miR-663b/ENDOU regulatory network was experimentally validated.
- MiR-663b promoted OSCC cell malignancy, and circ_0049396/ENDOU overexpression partially reversed these effects.
Conclusions:
- circ_0049396 inhibits OSCC malignant behavior by modulating the miR-663b/ENDOU axis.
- circ_0049396 demonstrates potential as a therapeutic agent for oral squamous cell carcinoma.
- Targeting the circ_0049396/miR-663b/ENDOU pathway could offer novel treatment strategies for OSCC.
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