LINC00222 regulates FOXO3 to interfere with β-catenin signaling pathway and suppresses prostate cancer progression

Sep 22, 2026

LINC00222 regulates FOXO3 to modulate the FOXO3/APC/β-catenin signaling cascade and suppress prostate cancer progression. Expression of LINC00222 and FOXO3 was measured by RT-qPCR, while cellular and tumor phenotypes were assessed using gain- and loss-of-function assays. Western blot, dual-luciferase reporter, bioinformatics, and immunoprecipitation assays were used to define the LINC00222–miR-19a–FOXO3–APC axis. LINC00222 and FOXO3 were downregulated in prostate cancer tissues and LINC00222 inhibited proliferation, metastasis, and promoted apoptosis via β-catenin pathway inhibition.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Prostate cancer burden and treatment challenges

Clinical biomarkers and prognostic needs

FOXO3 and signaling rationale

FOXO transcription factors in tumor biology

Study design and methods

Gene expression and functional assays

Molecular interaction analyses

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN LINC00222 regulates FOXO3 to interfere with β-catenin signaling pathway and suppresses prostate cancer progression Hui Li1,2􀀍, Wenfeng Zhao2, Yuyou Deng2, Zhongcheng Liu3􀀍, Jiameng Li3 & Shuoqi Tian3 FOXO3 has been confirmed to be closely involved in the occurrence and progression of prostate cancer. In this study, we aimed to investigate the potential mechanisms of FOXO3 in prostate cancer progression. The expression of LINC00222 and FOXO3 in non-cancerous tissues and cancer tissues was detected by RT-qPCR. LINC00222 roles in regulating cell function in vitro as well as tumorigenesis in vivo were detected by gain-of-function and loss-of-function assays. The key protein expression was detected by western blotting assay. Dual luciferase reporter assay, bioinformatics analysis and immunoprecipitation assay were used to analyze the relationship between LINC00222 and miR- 19a, miR-19a and FOXO3, or FOXO3 and APC. The results showed that the expression levels of both LINC00222 and FOXO3 were downregulated in prostate cancer tissues. In PC-3 cells, upregulation of FOXO3 significantly inhibited vimentin expression and promoted E-cadherin expression, as well as enhanced cell sensitivity to docetaxel. Compared to the control group, upregulation of LINC00222 in prostate cancer significantly inhibited cell proliferation and metastasis, and promoted cell apoptosis. Furthermore, LINC00222 competitively bound to miR-19a, enhanced FOXO3 expression, and then increased APC expression and inhibited the β-catenin signaling. Consistently, the in vivo experiments further confirmed the cancer inhibitory role of LINC00222 in prostate cancer. The present study revealed that LINC00222 adsorbed miR-19ato modulate FOXO3/APC/β-catenin signaling cascades and thereafter inhibited prostate cancer progression, which provided valuable insights into prostate cancer treatment. Keywords Prostate cancer, FOXO3, β-catenin, LINC00222, miR-19a Prostate cancer is the second most common cancer among men worldwide, and a leading cause of cancer-related deaths1,2. Prostate cancer is a highly heterogeneous disease, ranging from inert or slow-developing forms to highly aggressive or potentially fatal variants. Approximately 75% of patients present with localized prostate cancer, which has a 5-year survival rate of nearly 100%. However, approximately 10% of prostate cancer patients have metastatic spread, with a 5-year survival rate of only 30%3,4. In the early stage, prostate cancer is usually androgen-dependent prostate cancer (ADPC), and androgen deprivation therapy (ADT) is the mainstay of treatment5. Regrettably, the majority of prostate cancer patients eventually progress to androgen-independent prostate cancer (AIPC), which is resistant to ADT6,7. Recent studies have indicated that prostate cancer showed a shift towards higher grade and higher stage, along with an increased incidence of metastasis, most likely due to changes in screening guidelines8,9. This increased prevalence of metastatic prostate cancer and the dismal prognosis of these cases highlight the urgent need to elucidate the cancer pathogenesis and identify biomarkers for diagnosis, prognosis, and patient-specific treatment. Currently, several biomarkers are employed in clinical practice to facilitate risk stratification, prognostic evaluation, and the guidance of personalized treatment strategies in prostate cancer. For example, galectin-3 (Gal-3), a β-galactoside-binding protein, has multiple biological functions. It has been demonstrated to play important roles in tumor development processes through regulating cell proliferation, apoptosis, cell invasion, 1Department of emergency surgery, Peking University People’s Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing 100044, China. 2Department of urology, Peking University International Hospital, Beijing 102206, China. 3College of Pharmaceutical

FAQs

What was the main goal of the study on FOXO3 and LINC00222?

To investigate the potential mechanisms by which FOXO3 and LINC00222 contribute to prostate cancer progression.

How were LINC00222 and FOXO3 expression patterns assessed?

LINC00222 and FOXO3 expression in non-cancerous and cancer tissues was measured using RT-qPCR.

What pathway does LINC00222 influence to suppress prostate cancer progression?

LINC00222 binds miR-19a, increases FOXO3 expression, elevates APC expression, and inhibits the β-catenin signaling pathway, leading to cancer suppression.

Sep 22, 2026

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