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. 2024 Feb 8;24(1):104.
doi: 10.1186/s12905-024-02905-7.

LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma

Xiaofeng Zhou  1 , Zhizun Li  1 , Moyu Li  2
Affiliations

LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma

Xiaofeng Zhou et al. BMC Womens Health. .

Abstract

Background: This Study investigated the role of WWTR1-AS1 in cervical squamous cell carcinoma (CSCC).

Results: WWTR1-AS1 expression was upregulated in CSCC tissues. WWTR1-AS1 was predicted to interact with miR-136, whereas correlation analysis revealed that there was no close correlation between WWTR1-AS1 and miR-136 across CSCC samples. Moreover, WWTR1-AS1 and miR-136 did not regulate the expression of each other. In addition, overexpression of WWTR1-AS1 increased the expression levels of Notch3, which could be targeted by miR-136. Cell stemness analysis indicated that the overexpression of WWTR1-AS1 and Notch3 increased CSCC cell stemness and the capacity of CSCC cell to grow as spheroids. Overexpression of miR-136 decreased CSCC cell stemness and reversed the effects of overexpression of WWTR1-AS1 on Notch3 in CSCC cells.

Conclusion: Therefore, WWTR1-AS1 may upregulate Notch3 through miR-136 to increase cancer cell stemness in CSCC.

Keywords: CSCC; Notch3; Stemness; WWTR1-AS1; miR-136.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The expression of WWTR1-AS1 and miR-136 was altered in CSCC. The differential expression of WWTR1-AS1 (A) and miR-136 (B) was analyzed in paired CSCC and non-tumor tissues collected from the 60 CSCC patients. ***, p < 0.001. Survival data (disease-free) in TCGA dataset were explored using GEPIA (http://gepia.cancer-pku.cn/) to analyze the correlation between WWTR1-AS1 expression and the survival of CSCC patients. Kaplan-Meier curve were used by SPSS. p < 0.05 was considered as statistically significant (C)
Fig. 2
Fig. 2
WWTR1-AS1 and miR-136 were not significantly correlated with each other. Pearson’s correlation coefficient analysis was performed to analyze the correlation between the expression levels of WWTR1-AS1 and miR-136 across both CSCC (A) and non-tumor (B) tissues
Fig. 3
Fig. 3
WWTR1-AS1 and miR-136 interacted with each other but did not regulate the expression of each other. IntaRNA 2.0 was applied to predict the binding of WWTR1-AS1 to miR-136 (A), which was further confirmed by dual luciferase activity assay (B). SiHa cells were transfected with either WWTR1-AS1 expression vector or miR-136 mimic, and the overexpression of WWTR1-AS1 WT/MUT and miR-136 was confirmed by RT-qPCR (C). The role of WWTR1-AS1 WT/MUT and miR-136 in regulating the expression of each other was studied by performing RT-qPCR (D). Control (C) cells were untransfected cells. NC cells were miR-NC mimics - or empty vector-transfected cells. *, p < 0.05
Fig. 4
Fig. 4
The overexpression of WWTR1-AS1 upregulated the expression of Notch3 To test whether WWTR1-AS1 can sponge miR-136, the effects of WWTR1-AS1 and miR-136 overexpression on the expression nof Notch3, a target of miR-136, were analyzed by RT-qPCR (A) and Western blot analysis (B). Control (C) cells were untransfected cells. NC cells were miR-NC mimics - or empty vector-transfected cells. *, p < 0.05
Fig. 5
Fig. 5
WWTR1-AS1 increased SiHa cell stemness by regulating the miR-136/Notch3 axis. The effects of WWTR1-AS1, miR-136 and Notch3 overexpression on the stemness of SiHa cells were analyzed by performing stemness assay. Control (C) cells were untransfected cells. NC cells were miR-NC mimics - or empty vector-transfected cells. *, p < 0.05
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