---
title: "RUNX2 drives LUAD proliferation and autophagy via transcriptional activation of TMEM74"
id: "pubmed-42715886"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42715886"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42715886/"
doi: "10.1016/j.bbrc.2026.154547"
published_at: "2026-10-22T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# RUNX2 drives LUAD proliferation and autophagy via transcriptional activation of TMEM74
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42715886
- **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/42715886/)
- **DOI:** [10.1016/j.bbrc.2026.154547](https://doi.org/10.1016%2Fj.bbrc.2026.154547)
- **Published At:** 2026-10-22T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study examined the role of **TMEM74** in lung adenocarcinoma (**LUAD**) and its regulation by **RUNX2**, using in vitro LUAD cell lines and in vivo xenograft models. - Investigators found **TMEM74** expression was elevated in lung cancer patient samples and LUAD cell lines; higher expression associated with poorer survival. - Stable LUAD cell lines with TMEM74 knockdown and TMEM74 overexpression were constructed; the manipulated lines showed consistent effects on proliferation, colony formation and apoptosis. - TMEM74 overexpression increased the LC3II/I ratio, decreased p62 protein levels, and increased autolysosome formation; knockdown produced opposite autophagy markers. - Chemical blockade of autophagy with bafilomycin A1 abolished the pro-proliferative and anti-apoptotic phenotype driven by TMEM74 overexpression, indicating autophagy dependence. - Subcutaneous xenograft experiments showed that TMEM74 knockdown limited tumor growth and reduced intratumoral autophagic activity. - Gene expression analyses identified a positive correlation between **RUNX2** and **TMEM74** in LUAD; forced **RUNX2** expression upregulated TMEM74 mRNA. - Dual luciferase reporter assays indicated that **RUNX2** enhanced TMEM74 transcriptional activity in LUAD cells, and TMEM74 knockdown reversed RUNX2-driven proliferation, reduced apoptosis, and increased autophagosome formation. - The source did not report specific sample sizes, numerical effect sizes, detailed methods for assays, or statistical values in the abstract; those methodological details are not available in the provided text.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 4. # RUNX2 regulates cell proliferation, autophagy activity and apoptosis in LUAD cell via transcriptionally activating TMEM74 [Ji Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#full-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Yuan-Zhuang Xia](https://pubmed.ncbi.nlm.nih.gov/?term=Xia+YZ&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#full-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Bo Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+B&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#full-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Yong He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42715886)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#full-view-affiliation-2 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. Electronic address: dlwuyuan81880401@163.com.") Affiliations Expand ### Affiliations * 1 Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. * 2 Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. Electronic address: dlwuyuan81880401@163.com. * PMID: **42715886** * DOI: [ 10.1016/j.bbrc.2026.154547 ](https://doi.org/10.1016/j.bbrc.2026.154547) Item in Clipboard # RUNX2 regulates cell proliferation, autophagy activity and apoptosis in LUAD cell via transcriptionally activating TMEM74 Ji Zhang et al. Biochem Biophys Res Commun. 2026. Show details Display options Display options Format Abstract PubMed PMID Biochem Biophys Res Commun Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biochem+Biophys+Res+Commun%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Biochem+Biophys+Res+Commun%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42715886/) . 2026 Oct 22:836:154547. doi: 10.1016/j.bbrc.2026.154547. Epub 2026 Sep 4. ### Authors [Ji Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+J&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#short-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Yuan-Zhuang Xia](https://pubmed.ncbi.nlm.nih.gov/?term=Xia+YZ&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#short-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Bo Huang](https://pubmed.ncbi.nlm.nih.gov/?term=Huang+B&cauthor_id=42715886)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#short-view-affiliation-1 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China."), [Yong He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Y&cauthor_id=42715886)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42715886/#short-view-affiliation-2 "Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. Electronic address: dlwuyuan81880401@163.com.") ### Affiliations * 1 Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. * 2 Department of Thoracic Surgery, The Fifth People's Hospital of Dalian, Dalian, PR China. Electronic address: dlwuyuan81880401@163.com. * PMID: **42715886** * DOI: [ 10.1016/j.bbrc.2026.154547 ](https://doi.org/10.1016/j.bbrc.2026.154547) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Lung cancer has the highest mortality rate of all cancers, and lung adenocarcinoma (LUAD) is one of the most common subtypes. TMEM74 expression is upregulated in both lung cancer patients and LUAD cell lines, and its high expression correlates with poor patient survival. Targeted TMEM74 knockdown and overexpression vectors were successfully constructed, and stably transfected LUAD cell lines were established. TMEM74 was found to significantly enhance LUAD cell proliferation and colony formation while suppressing apoptosis. TMEM74 overexpression elevated the LC3II/I ratio, reduced p62 levels, and boosted autolysosome formation, whereas TMEM74 knockdown exerted opposite effects. Bafilomycin A1-mediated autophagy inhibition abrogated the pro-proliferative and anti-apoptotic effects driven by TMEM74 overexpression. Subcutaneous xenograft experiments revealed that TMEM74 knockdown restrained tumor growth, and impaired autophagic activity in tumor. A positive correlation was observed between the expression levels of Runt-related transcription factor 2 (RUNX2) and TMEM74 in LUAD. RUNX2 overexpression in LUAD cells induced upregulation of TMEM74 mRNA levels. Dual luciferase reporter assays demonstrated that RUNX2 significantly enhanced the transcriptional activity of TMEM74 in LUAD cells. TMEM74 knockdown reversed the increased cell proliferation, reduced apoptosis and enhanced autophagosome formation induced by RUNX2 overexpression in LUAD cells. Collectively, our experimental results demonstrate that RUNX2 transcriptionally activates TMEM74, thereby promoting LUAD cell proliferation and autophagy and inhibiting cell apoptosis in vitro; TMEM74 knockdown suppresses tumor growth in vivo. **Keywords:** Apoptosis; Autophagy; Lung adenocarcinoma; RUNX2; TMEM74. Copyright © 2026 Elsevier Inc. All rights reserved. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ## Similar articles * [ [miR-1910-3p affects proliferation, invasion and in vivo tumor growth of lung adenocarcinoma by inducing epithelial-mesenchymal transition]. ](https://pubmed.ncbi.nlm.nih.gov/42331548/) Fang MX, Yu XX, Huang JF, Wu WD.Fang MX, et al.Zhonghua Zhong Liu Za Zhi. 2026 Jun 23;48(6):783-792. doi: 10.3760/cma.j.cn112152-20250714-00335.Zhonghua Zhong Liu Za Zhi. 2026.PMID: 42331548Chinese. * [ Caveolin-1 inhibits the proliferation and invasion of lung adenocarcinoma via EGFR degradation. ](https://pubmed.ncbi.nlm.nih.gov/40594106/) Dong J, Du R, Zhang Y, Hong B, Sun G.Dong J, et al.Sci Rep. 2025 Jul 1;15(1):21654. doi: 10.1038/s41598-025-05259-8.Sci Rep. 2025.PMID: 40594106Free PMC article. * [ Long noncoding RNA LINC01106 promotes lung adenocarcinoma progression via upregulation of autophagy. ](https://pubmed.ncbi.nlm.nih.gov/39735666/) Sun G, Zheng Y, Cai J, Gao J, Dong L, Zhang X, Huang Y.Sun G, et al.Oncol Res. 2024 Dec 20;33(1):171-184. doi: 10.32604/or.2024.047626. eCollection 2025.Oncol Res. 2024.PMID: 39735666Free PMC article. * [ New link between RNH1 and E2F1: regulates the development of lung adenocarcinoma. ](https://pubmed.ncbi.nlm.nih.gov/38783241/) Zhao W, Liu Y, Yang Y, Wang L.Zhao W, et al.BMC Cancer. 2024 May 24;24(1):635. doi: 10.1186/s12885-024-12392-6.BMC Cancer. 2024.PMID: 38783241Free PMC article. * [ Silencing CACYBP suppresses lung adenocarcinoma growth via CDK1 inhibition. ](https://pubmed.ncbi.nlm.nih.gov/40167359/) Wen G, Niu S, Mei S, Wang S.Wen G, et al.Biomol Biomed. 2025 Jul 31;25(8):1801-1815. doi: 10.17305/bb.2025.11849.Biomol Biomed. 2025.PMID: 40167359Free PMC article. [ See all similar articles ](https://pubmed.ncbi.nlm.nih.gov/?linkname=pubmed_pubmed&from_uid=42715886) ## MeSH terms * Adenocarcinoma of Lung* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenocarcinoma+of+Lung%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenocarcinoma+of+Lung) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42715886/) * Adenocarcinoma of Lung* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenocarcinoma+of+Lung%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adenocarcinoma+of+Lung) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42715886/) * Adenocarcinoma of Lung* / pathology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adenocarcinoma+of+Lung%2Fpathology%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH 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