STAT3 exerts pro-tumor and anti-autophagy roles in cervical cancer

Lin Wu,Ke Zhang,Huirong Zhang,Zhenyu Zu,Bowen Shen,Dongxiang Shen,Yao Yang,Junpeng Li,Min Luo

doi:10.1186/s13000-021-01182-4

Abstract

BackgroundSTAT3 plays an important role in cervical cancer. LC3B, the most potential molecular biomarker of autophagy that may promote or inhibit cancer progression, can be downregulated by STAT3. However the role of STAT3 in the autophagy of cervical cancer remains unclear.PurposeThis study aimed to evaluate the relationship between STAT3 and LC3B in protein level, and verify whether STAT3 promotes proliferation, migration and plate colony formation by inhibiting autophagy of cervical cancer cells through bcl2-beclin1 axis.ResultsSTAT3 was overexpressed in cervical cancer tissues, and negatively correlated with the expression level of LC3B. STAT3 knockout or knockdown significantly increased the autophagy level and decreased proliferation, migration, plate colony formation and subcutaneous tumorigenesis of cervical cancer cells in vitro and in vivo. STAT3 is known to mediate autophagy through Bcl2-Beclin1 complex. Bcl2 was positively whereas Beclin1 negatively correlated with STAT3 expression, indicating that Bcl2-Beclin1 complex involved in this transition.ConclusionSTAT3 may upregulate the autophagy level of cervical cancer cells through the Bcl2-Beclin1 axis. This indicates that STAT3 may be an important prognostic and therapeutic target for cervical cancer.

Highlights

Cervical cancer is the second leading cause of cancerrelated death among women in developing countries, and has a high recurrence rate and drug resistance [1]
Signal transducer and activator of transcription 3 (STAT3) may upregulate the autophagy level of cervical cancer cells through the Bcl2-Beclin1 axis
STAT3 is highly expressed in cervical cancer patients and is negatively correlated with LC3B In order to explore the role of STAT3 in the progression of cervical cancer, we first analyzed the relationship between the expression of STAT3 and LC3B

Summary

Introduction

Cervical cancer is the second leading cause of cancerrelated death among women in developing countries, and has a high recurrence rate and drug resistance [1]. Numerous studies report [4,5,6] that STAT3 could affect autophagy through modifying the key molecular such as LC3B and affect the progression of the tumor. There were studies [7,8,9] implied that autophagy is closely related to the proliferation, differentiation and metastasis of numerous cancer cells. STAT3 in the nucleus could be the main transcriptional enhancer of several genes, such as BCL2, BECN1, PIK3C3, CTSB, CTSL, that inhibit or activate cell autophagy. LC3B, the most potential molecular biomarker of autophagy that may promote or inhibit cancer progression, can be downregulated by STAT3. Purpose: This study aimed to evaluate the relationship between STAT3 and LC3B in protein level, and verify whether STAT3 promotes proliferation, migration and plate colony formation by inhibiting autophagy of cervical cancer cells through bcl2-beclin axis

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