ONCOLOGY REPORTS - 56 - Effect of the miR-26a/b-5p-STAT3-YKL-40 regulatory axis on proliferation, migration, and invasion of endometrial cancer cells

Sep 22, 2026

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Endometrial cancer incidence continues to increase, making timely diagnosis and effective targeted therapy essential. This study validated how STAT3 influences endometrial cancer (EC) phenotypes and mapped its regulatory mechanisms upstream and downstream. STAT3 expression in EC tissues was assessed by immunohistochemistry, and dual luciferase assays confirmed regulation between STAT3 and miR-26a/b-5p. Functional effects on HEC-1A cells were measured using CCK-8, scratch, and Transwell assays, while co-immunoprecipitation verified STAT3–CHI3L1/YKL-40 binding. Results showed high STAT3 associated with progression, miR-26a/b-5p directly targeting STAT3, STAT3 promoting proliferation, migration, and invasion, and STAT3 inducing YKL-40 expression.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

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Abstract

Introduction

STAT3 in cancer progression

miRNAs and the STAT3 regulatory axis

ONCOLOGY REPORTS 56: 127, 2026 Effect of the miR‑26a/b‑5p‑STAT3‑YKL‑40 regulatory axis on proliferation, migration, and invasion of endometrial cancer cells * * * XINZHAO SUN , SHANSHAN LIN , XUEYAN ZHONG , YANLU LUO, JIAHUANG YANG and JIANGTAO FAN Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China Received September 30, 2025; Accepted April 6, 2026 DOI: 10. 3892/or.2026.9132 Abstract. The incidence of endometrial cancer (EC) is on the rise annually, emphasizing the importance of timely diagnosis and treatment. Signal transducer and activator of transcription 3 (STAT3) has been identified as a proto‑oncogene involved in multiple signaling pathways affecting various biological processes, especially in tumours. The aim of the present study was to validate the impact of STAT3 on EC phenotype and investigate its upstream and downstream regulatory mecha‑ nisms. Immunohistochemical analysis was conducted to assess STAT3 expression in EC tissues, followed by dual luciferase assays to confirm the regulatory relationship between STAT3 and microRNA (miR)‑26a/b‑5p. The effects of STAT3 and miR‑26a/b‑5p on HEC‑1A cell proliferation and metastasis were evaluated through Cell Counting Kit‑8 assays, cell scratch assays, and Transwell assays. Co‑immunoprecipitation assays verified the binding between STAT3 and chitinase‑3‑like protein 1 (CHI3L1, also known as YKL‑40) . The results demonstrated high STAT3 expression in EC, associated with disease progression. miR‑26a/b‑5p directly targeted STAT3 . Upregulated STAT3 enhanced HEC‑1A cell proliferation, migration, and invasion, counteracting the inhibitory effects of miR‑26a/b‑5p on cell migration and invasion. In addition, it was confirmed that STAT3 binds to and promotes the expres‑ sion of YKL‑40 . These findings contribute to clarifying the pathogenesis of EC. Correspondence to: Dr Jiangtao Fan, Department of Gynecology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi 530021, P.R. China E‑mail: [jt_fan2018@163.com](jt_fan2018@163.com) *Contributed equally Abbreviations: CHI3L1 and YKL‑40, chitinase‑3‑like protein 1; EC, endometrial cancer; JAK, Janus kinase; STAT3, signal transducer and activator of transcription 3; TILs, tumor‑infiltrating lymphocytes; VEGF, vascular endothelial growth factor Key words: endometrial cancer, STAT3, microRNA‑26a‑5p, microRNA‑26b‑5p, chitinase‑3‑like protein 1 Introduction Endometrial cancer (EC) is a gynecological cancer character‑ ized by a rapidly increasing global incidence and associated mortality rate. According to statistics, there were over 420,000 new cases of corpus uteri cancer worldwide in 2022 (1) . While EC predominantly affects postmenopausal women, there is arising incidence among younger women. Early detection and diagnosis of EC at the low‑grade stage have been revealed tobe associated with a favorable prognosis, whereas diagnosis at the advanced stages has been associated with a reduced chance of survival (2,3) . The STAT3 protein with 770 amino acids regulates cell survival, differentiation, and proliferation. Notably, STAT3 has been shown to contribute to the development of cancers, such as myeloma, as well as breast and lung cancers due to its inherent ability to enhance proliferation and metastasis of tumor cells, as well as induce chemo‑resistance and immune suppression. In human cancers, over‑activation of STAT3 has been demon‑ strated tobe associated with dismal outcomes (4‑6). Specifically, STAT3 has been shown to regulate invasion, proliferation, drug resistance, and angiogenesis of EC cells. Research has estab‑ lished that angiogenesis is a crucial process in the development of tumors. Vascular cancer‑associated fibroblasts, which are components of the tumor microenvironment, facilitate angio‑ genesis by promoting the expression of vascular endothelialcadherin and Vimentin, as well as

FAQs

What is the study’s primary goal regarding STAT3 in endometrial cancer?

To validate STAT3’s impact on endometrial cancer phenotype and to investigate upstream and downstream regulatory mechanisms, including its relationship with miR-26a/b-5p.

How did the researchers confirm the regulatory relationship between STAT3 and miR-26a/b-5p?

Immunohistochemistry assessed STAT3 expression in EC tissues, and dual luciferase assays confirmed regulation between STAT3 and miR-26a/b-5p.

What effects did STAT3 and miR-26a/b-5p have on EC cell behavior?

Upregulated STAT3 enhanced HEC-1A cell proliferation, migration, and invasion, counteracting the inhibitory effects of miR-26a/b-5p on migration and invasion.

Sep 22, 2026

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