Downregulation of LRRC59 suppresses cervical cancer progression likely by inhibiting YBX1-mediated Wnt/β-catenin signaling

Sep 22, 2026

Leucine-rich repeat-containing protein 59 (LRRC59) is examined in cervical cancer to clarify its functional role and molecular mechanisms. LRRC59 expression is evaluated in cervical cancer and normal tissues using public databases and clinical specimens, with correlations analyzed against clinical features and survival. LRRC59 knockdown suppresses proliferation, invasion, and migration while promoting apoptosis in vitro and in xenograft models. Mechanistically, LRRC59 inhibition reduces β-catenin and downstream c-Myc/cyclin D1 and lowers YBX1, with Wnt/β-catenin agonist SKL2001 partially reversing the effects.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Background

Clinical context of cervical cancer

LRRC59 biology and prior findings

Wnt/β-catenin pathway and YBX1

Study findings

LRRC59 expression and prognosis association

Functional effects of LRRC59 knockdown

Mechanistic link via β-catenin/c-Myc/cyclin D1 and YBX1

Pathway rescue with SKL2001

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Downregulation of LRRC59 suppresses cervical cancer progression likely by inhibiting YBX1-mediated Wnt/β-catenin signaling Qian Zhu1,2,3, Guiqin Xu2, Tianming Wang4, Zhuyun Ding5, Lianhua Liu2,3, Ling Ling2􀀍 & Xiaoyan Ying1􀀍 Leucine-rich repeat-containing protein 59 (LRRC59) has been implicated in the pathogenesis of various human cancers, but its functional role and underlying molecular mechanisms in cervical carcinogenesis and progression remain unknown. In this study, LRRC59 expression was assessed in cervical cancer (CC) and normal cervical tissues using public databases and clinical specimens. Correlations between LRRC59 expression and clinical characteristics were analyzed using data from our institutional cohort and The Cancer Genome Atlas (TCGA). The functional effects of LRRC59 on CC cell proliferation, apoptosis, invasion, and migration were evaluated through in vitro assays and xenograft tumor models. Potential mechanisms were identified by integrated bioinformatics analysis and subsequently validated experimentally. LRRC59 was significantly upregulated in CC tissues, and elevated LRRC59 expression correlated with poor prognosis. Knockdown of LRRC59 suppressed CC cell proliferation, invasion, and migration, while promoting apoptosis. Mechanistically, LRRC59 knockdown downregulated total β-catenin, nuclear β-catenin, and the expression of downstream targets c-Mycand cyclin D1. Treatment with SKL2001, aWnt/β-catenin pathway agonist, partially reversed the inhibitory effects of LRRC59 knockdown on proliferation, invasion, and migration, as well as its proapoptotic effect. Furthermore, LRRC59 knockdown led to reduced expression of Y-box binding protein 1 (YBX1). Collectively, these findings demonstrate that LRRC59 promotes CC progression likely via YBX1-mediated Wnt/β-catenin signaling, identifying LRRC59 as a promising prognostic biomarker and potential therapeutic target in cervical cancer. Keywords LRRC59, Cervical cancer, YBX1, Wnt/β-catenin signaling pathway, Prognosis Cervical cancer (CC) remains a major global health burden, ranking as the fourth most common cause of cancer incidence and mortality among women worldwide1. Current management of CCis guided by clinical staging. Early-stage disease is typically treated with surgical resection followed by adjuvant therapy when indicated, whereas concurrent chemoradiation represents the standard approach for advanced cases. For recurrent or metastatic CC, chemotherapy and immune-targeted agents play crucial roles in treatment strategies. Although patients diagnosed at an early stage generally have favorable outcomes, a substantial number of cases are detected at advanced stages, with approximately 52% presenting with local invasion or distant metastasis at initial diagnosis, leading to poor prognosis2. Therefore, a deeper understanding of the molecular mechanisms driving cervical carcinogenesis and exploring novel therapeutic approaches are of great clinical importance. 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, China. 2Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital, Nanjing Medical University, Nanjing 211100, Jiangsu, China. 3Jiangning Clinical Medical School, Kangda College of Nanjing Medical University, Nanjing 211100, Jiangsu, China. 4Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, Jiangsu, China. 5Department of Obstetrics and Gynecology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China. 􀀍 email: [lingling_7430@sina.com](lingling_7430@sina.com); [xiaoyanying0267@njmu.edu.cn](xiaoyanying0267@njmu.edu.cn) [www. nature.com/scientificreports](www. nature.com/scientificreports) Leucine-rich repeat-containing protein 59

FAQs

How does LRRC59 expression relate to cervical cancer progression and prognosis?

LRRC59 is significantly upregulated in cervical cancer tissues, and higher LRRC59 expression correlates with poor patient prognosis.

What cellular behaviors are affected by LRRC59 knockdown?

LRRC59 knockdown suppresses cervical cancer cell proliferation, invasion, and migration, and it promotes apoptosis.

What mechanism explains LRRC59’s effect on cervical cancer cells?

LRRC59 promotes progression likely through YBX1-mediated Wnt/β-catenin signaling, reducing total and nuclear β-catenin and downstream c-Myc and cyclin D1 when LRRC59 is inhibited.

Sep 22, 2026

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