---
title: "BBOX1-AS1 as a Biomarker and Regulator of Tumor Cell Proliferation in NSCLC"
id: "pubmed-42764220"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42764220"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42764220/"
doi: "10.3760/cma.j.cn112152-20250720-00351"
published_at: "2026-09-23T00:00:00.000Z"
evidence_level: "English Abstract"
license: "CC-BY-NC-4.0 / Informational Use"
---
# BBOX1-AS1 as a Biomarker and Regulator of Tumor Cell Proliferation in NSCLC
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42764220
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42764220/)
- **DOI:** [10.3760/cma.j.cn112152-20250720-00351](https://doi.org/10.3760%2Fcma.j.cn112152-20250720-00351)
- **Published At:** 2026-09-23T00:00:00.000Z
- **Evidence Rating:** English Abstract
## Executive GIST (TL;DR)
- The study evaluated **BBOX1-AS1** expression in non-small cell lung cancer (**NSCLC**) tissues, serum, and cell lines using RT-qPCR and found significant upregulation in tumors, serum, and cell lines (P < 0.05). - High **BBOX1-AS1** expression correlated with larger tumor diameter, lymph node metastasis, and advanced TNM stage (all P < 0.05). - Patients with high BBOX1-AS1 expression had lower 5-year survival (36.7%) versus low expression (61.1%); high BBOX1-AS1 was an independent prognostic factor (HR = 0.496, 95% CI: 0.272–0.904, P = 0.022). - Serum **miR-3940-3p** was downregulated in NSCLC (P < 0.05) and negatively correlated with BBOX1-AS1 levels (r = -0.646, P < 0.001). - Both BBOX1-AS1 (AUC = 0.858) and miR-3940-3p (AUC = 0.852) showed high diagnostic value for NSCLC by ROC analysis. - Knockdown of BBOX1-AS1 reduced proliferation of A549 cells in CCK-8 assays (72 h absorbance: siRNA group 0.67 ± 0.05 vs Mock 1.17 ± 0.06 and siRNA-NC 1.06 ± 0.03; P < 0.001). - Dual-luciferase assays indicated that **miR-3940-3p** interacts directly with BBOX1-AS1 and may mediate its function. - Bioinformatics predicted ten potential miR-3940-3p target genes: MOV10, TP53, PABPC1, TIAL1, STAU1, IGF2BP1, FMR1, ELAVL1, CPEB1, and PABPN1. - The authors conclude that high **BBOX1-AS1** expression in NSCLC signals poorer prognosis and that BBOX1-AS1 knockdown reduces tumor cell proliferation, suggesting BBOX1-AS1 as a candidate prognostic biomarker and therapeutic target.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliation * 1 Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China. * PMID: **42764220** * DOI: [ 10.3760/cma.j.cn112152-20250720-00351 ](https://doi.org/10.3760/cma.j.cn112152-20250720-00351) Item in Clipboard # [Preliminary exploration of BBOX1-AS1 as a potential biomarker involved in the regulation of tumor cell proliferation in non-small cell lung cancer] [Article in Chinese] X W Zeng et al. Zhonghua Zhong Liu Za Zhi. 2026. Show details Display options Display options Format Abstract PubMed PMID Zhonghua Zhong Liu Za Zhi Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Zhonghua+Zhong+Liu+Za+Zhi%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Zhonghua+Zhong+Liu+Za+Zhi%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42764220/) . 2026 Sep 23;48(9):1147-1156. doi: 10.3760/cma.j.cn112152-20250720-00351. ### Authors [X W Zeng](https://pubmed.ncbi.nlm.nih.gov/?term=Zeng+XW&cauthor_id=42764220)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42764220/#short-view-affiliation-1 "Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China."), [H F Luo](https://pubmed.ncbi.nlm.nih.gov/?term=Luo+HF&cauthor_id=42764220)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42764220/#short-view-affiliation-1 "Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China."), [X Y He](https://pubmed.ncbi.nlm.nih.gov/?term=He+XY&cauthor_id=42764220)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42764220/#short-view-affiliation-1 "Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China."), [K Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+K&cauthor_id=42764220)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42764220/#short-view-affiliation-1 "Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China."), [T P Guo](https://pubmed.ncbi.nlm.nih.gov/?term=Guo+TP&cauthor_id=42764220)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42764220/#short-view-affiliation-1 "Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China.") ### Affiliation * 1 Department of Cardiothoracic Surgery, Pangang Group General Hospital, Panzhihua 617023, China. * PMID: **42764220** * DOI: [ 10.3760/cma.j.cn112152-20250720-00351 ](https://doi.org/10.3760/cma.j.cn112152-20250720-00351) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract in [ English, ](https://pubmed.ncbi.nlm.nih.gov/42764220/#eng-abstract) [ Chinese ](https://pubmed.ncbi.nlm.nih.gov/42764220/#zho-abstract) **Objective:** To assess the clinical value of differential expression of BBOX1-AS1 in non-small cell lung cancer (NSCLC), and to explore its function and mechanism in disease progression through regulating tumor cells. **Methods:** Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of BBOX1-AS1. The chi-square test was used to analyze the relationship between BBOX1-AS1 and clinicopathological characteristics of patients (patients diagnosed with NSCLC at Pangang Group General Hospital from January 2018 to January 2021). The clinical diagnostic value of BBOX1-AS1 and miR-3940-3p was evaluated by receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve and Cox regression analysis were used to evaluate the prognostic value of BBOX1-AS1. Cell counting kit-8 (CCK-8) assay was used to analyze the effect of BBOX1-AS1 on the biological function of tumor cells. Bioinformatics tools and dual luciferase reporter system were used to investigate the downstream miRNAs and target genes mediating the function of BBOX1-AS1. **Results:** BBOX1-AS1 expression was significantly upregulated in NSCLC tumor tissues, serum, and cell lines (all _P_ ＜0.05). High BBOX1-AS1 expression was significantly correlated with larger tumor diameter, lymph node metastasis, and advanced TNM stage (all _P_ ＜0.05). NSCLC patients with high BBOX1-AS1 expression had a significantly lower 5-year survival rate (36.7%) than those with low expression (61.1%), and high BBOX1-AS1 expression was identified as an independent prognostic factor for NSCLC (_HR_ =0.496, 95% _CI_ : 0.272, 0.904, _P_ =0.022). MiR-3940-3p expression was downregulated in NSCLC serum (_P_ ＜0.05) and negatively correlated with BBOX1-AS1 levels (_r_ =-0.646,_P_ ＜0.001). Both BBOX1-AS1 [area under the curve (AUC)=0.858] and miR-3940-3p (AUC=0.852) exhibited high diagnostic value for NSCLC. Knockdown of BBOX1-AS1 inhibited A549 cell proliferation [the absorbance value of the BBOX1-AS1-siRNA group at 72 hours was 0.67±0.05, which was lower than those of the Mock group (1.17±0.06) and the siRNA-NC group (1.06±0.03), _P_ ＜0.001]. MiR-3940-3p directly interacted with BBOX1-AS1 and might be involved in mediating the function of BBOX1-AS1. Bioinformatics analysis predicted 10 potential target genes of miR-3940-3p: _MOV10_ , _TP53_ , _PABPC1_ , _TIAL1_ , _STAU1_ , _IGF2BP1_ , _FMR1_ , _ELAVL1_ , _CPEB1_ , and _PABPN1_. **Conclusions:** BBOX1-AS1 is highly expressed in NSCLC patients, and its high expression indicates a poor prognosis. Knockdown of BBOX1-AS1 leads to a decrease in tumor cell proliferation. This study screens potential functional target genes and prognostic biomarkers for NSCLC. **目的：** 评估BBOX1-AS1的差异表达在非小细胞肺癌（NSCLC）中的临床价值，探讨其通过调控肿瘤细胞参与疾病进展的功能和机制。 **方法：** 实时荧光定量聚合酶链反应检测BBOX1-AS1的表达情况， _χ_ 2检验分析BBOX1-AS1与患者（2018年1月至2021年1月于攀钢集团总医院确诊NSCLC的患者）临床病理学特征的关系。通过受试者操作特征曲线评估BBOX1-AS1和miR-3940-3p的临床诊断价值。绘制Kaplan-Meier生存曲线并进行Cox回归分析，评估BBOX1-AS1的预后价值。通过细胞计数试剂盒8实验分析BBOX1-AS1对肿瘤细胞生物学功能的影响。利用生物信息学工具和双荧光素酶报告系统探究介导BBOX1-AS1功能发挥的下游miRNAs及靶基因。 **结果：** BBOX1-AS1在NSCLC肿瘤组织、血清中表达显著上调（均 _P_ ＜0.05），高水平BBOX1-AS1与较大的肿瘤长径、淋巴结转移及TNM晚期有关（均 _P_ ＜0.05）。高表达BBOX1-AS1的NSCLC患者5年生存率（36.7%）显著低于低表达组（61.1%），BBOX1-AS1高表达是NSCLC的独立预后因子（ _HR_ =0.496，95% _CI_ ：0.272～0.904， _P_ =0.022）。miR-3940-3p在NSCLC血清中表达下调（ _P_ ＜0.05），与BBOX1-AS1表达水平呈负相关（ _r_ =-0.646， _P_ ＜0.001）。BBOX1-AS1［曲线下面积（AUC）=0.858］与miR-3940-3p（AUC=0.852）均具有较高的NSCLC诊断价值。抑制BBOX1-AS1的表达抑制A549细胞增殖［72 h时BBOX1-AS1-siRNA组吸光度值为0.67±0.05，低于Mock组（1.17±0.06）、siRNA-NC组（1.06±0.03）， _P_ ＜0.001］。miR-3940-3p与BBOX1-AS1直接互作，可能参与BBOX1-AS1的功能发挥。生物信息学分析预测了miR-3940-3p的10个热点靶基因：MOV10、TP53、PABPC1、TIAL1、STAU1、IGF2BP1、FMR1、ELAVL1、CPEB1、PABPN1。 **结论：** BBOX1-AS1在NSCLC患者中高表达，且BBOX1-AS1的高表达提示NSCLC患者的不良预后。抑制BBOX1-AS1的表达可抑制肿瘤细胞增殖。. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement 所有作者声明无利益冲突 ## Similar articles * [ LncRNA NNT-AS1 promotes non-small cell lung cancer progression through regulating miR-22-3p/YAP1 axis. ](https://pubmed.ncbi.nlm.nih.gov/31923353/) He W, Zhang Y, Xia S.He W, et al.Thorac Cancer. 2020 Mar;11(3):549-560. doi: 10.1111/1759-7714.13280. Epub 2020 Jan 10.Thorac Cancer. 2020.PMID: 31923353Free PMC article. * [ LncRNA CCDC144NL-AS1 Serves as a Prognosis Biomarker for Non-small Cell Lung Cancer and Promotes Cellular Function by Targeting miR-490-3p. ](https://pubmed.ncbi.nlm.nih.gov/34115289/) Zhang L, Chi B, Chai J, Qin L, Zhang G, Hua P, Jin C.Zhang L, et al.Mol Biotechnol. 2021 Oct;63(10):933-940. doi: 10.1007/s12033-021-00351-6. 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