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Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long
Yu-Xin Zhao1, Yan Cui2, Xin-Hong Li3
1Department of Anesthesiology, Inner Mongolia Chest Hospital, The Fourth Hospital, Hohhot 010035, Inner Mongolia Autonomous Region, China.
Background:
Colorectal cancer has a low 5-year survival rate and high mortality. Human β-defensin-1 (hBD-1) may play an integral function in the innate immune system, contributing to the recognition and destruction of cancer cells. Long non-coding RNAs (lncRNAs) are involved in the process of cell differentiation and growth.
Aim:
To investigate the effect of hBD-1 on the mammalian target of rapamycin (mTOR) pathway and autophagy in human colon cancer SW620 cells.
Methods:
CCK8 assay was utilized for the detection of cell proliferation and determination of the optimal drug concentration. Colony formation assay was employed to assess the effect of hBD-1 on SW620 cell proliferation. Bioinformatics was used to screen potentially biologically significant lncRNAs related to the mTOR pathway. Additionally, p-mTOR (Ser2448), Beclin1, and LC3II/I expression levels in SW620 cells were assessed through Western blot analysis.
Results:
hBD-1 inhibited the proliferative ability of SW620 cells, as evidenced by the reduction in the colony formation capacity of SW620 cells upon exposure to hBD-1. hBD-1 decreased the expression of p-mTOR (Ser2448) protein and increased the expression of Beclin1 and LC3II/I protein. Furthermore, bioinformatics analysis identified seven lncRNAs (2 upregulated and 5 downregulated) related to the mTOR pathway. The lncRNA TCONS_00014506 was ultimately selected. Following the inhibition of the lncRNA TCONS_00014506, exposure to hBD-1 inhibited p-mTOR (Ser2448) and promoted Beclin1 and LC3II/I protein expression.
Conclusion:
hBD-1 inhibits the mTOR pathway and promotes autophagy by upregulating the expression of the lncRNA TCONS_00014506 in SW620 cells.
Insights
Human beta-defensin-1 (hBD-1) inhibits colon cancer cell growth by targeting the mTOR pathway and promoting autophagy. This effect is mediated by the upregulation of the long non-coding RNA TCONS_00014506.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Colorectal cancer (CRC) exhibits high mortality and low survival rates.
- Human beta-defensin-1 (hBD-1) is implicated in innate immunity and cancer cell recognition.
- Long non-coding RNAs (lncRNAs) regulate cellular processes like differentiation and growth.
Purpose of the Study:
- To investigate the impact of hBD-1 on the mammalian target of rapamycin (mTOR) pathway.
- To examine the effect of hBD-1 on autophagy in human colon cancer SW620 cells.
- To identify lncRNAs associated with the mTOR pathway in CRC.
Main Methods:
- Cell proliferation was assessed using CCK8 and colony formation assays.
- Bioinformatics analysis screened lncRNAs linked to the mTOR pathway.
- Western blot quantified protein levels of p-mTOR, Beclin1, and LC3II/I.
Main Results:
- hBD-1 significantly inhibited SW620 cell proliferation and colony formation.
- hBD-1 decreased p-mTOR expression while increasing Beclin1 and LC3II/I levels.
- Seven mTOR-related lncRNAs were identified; TCONS_00014506 inhibition modulated hBD-1's effects.
Conclusions:
- hBD-1 inhibits the mTOR pathway and induces autophagy in SW620 cells.
- Upregulation of lncRNA TCONS_00014506 mediates hBD-1's anti-cancer effects.
- hBD-1 represents a potential therapeutic target for colorectal cancer.
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