TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts

Kim, EunGi; Kim, Wanyeon; Lee, Sung-Min; Chun, Jahyun; Kang, JiHoon; Park, Gaeul; Han, IkJoon; Yang, Hee Jung; Youn, HyeSook; Youn, BuHyun

doi:10.1038/s41598-017-09447-z

Cited by 34 publications

(31 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, NF-κB pathway was reported to facilitate ESCC cell proliferation and invasion [33]. The previous studies have pointed out that TRAF4 could activate NF-κB to accelerate cancer development [34,35]. In present study, we identified that ZFPM2-AS1 could activate NF-κB pathway via up-regulating TRAF4, thus facilitating ESCC cell proliferation, migration, invasion and inhibiting ESCC cell apoptosis.…”

supporting

confidence: 48%

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

Sun

2020

Bioscience Reports

View full text Add to dashboard Cite

Emerging evidence has confirmed that long noncoding RNAs (lncRNAs) are strongly involved in tumor initiation and development. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) has been identified as a tumor facilitator in some cancers; nevertheless, its functional significance and regulatory mechanism remain greatly unclear in esophageal squamous cell carcinoma (ESCC). Here, we detected ZFPM2-AS1 expression in ESCC cell lines using qRT-PCR. ZFPM2-AS1 knockdown models were established for investigating the biological function of ZFPM2-AS1 in ESCC cells. The association between miR-3612 and ZFPM2-AS1 or TRAF4 was assessed by RNA pull-down and luciferase reporter assays. The present study indicated that ZFPM2-AS1 was significantly up-regulated in ESCC cells. Functional assays manifested that ZFPM2-AS1 knockdown restrained cell proliferation, migration and invasion, and facilitated cell apoptosis in ESCC. Mechanistically, ZFPM2-AS1 promoted ESCC cell growth and up-regulated TRAF4 to trigger NF-κB pathway by sequestering miR-3612. Besides, miR-3612 was confirmed to be a tumor inhibitor in ESCC. Through restoration experiments, we observed that TRAF4 overexpression could recover the suppressive effect of ZFPM2-AS1 on ESCC cell growth. Collectively, all the results suggested that ZFPM2-AS1 was an oncogene in ESCC cell growth by up-regulating TRAF4 and activating NF-κB pathway.

show abstract

supporting

confidence: 48%

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

Sun

2020

Bioscience Reports

View full text Add to dashboard Cite

show abstract

“…Moreover, the tumor-facilitator role of TRAF4 has been validated in hepatocellular carcinoma [34], intrahepatic cholangiocarcinoma [35], breast cancer [36], and colon cancer [37]. More importantly, TRAF4 is confirmed to promote the development of lung cancer [38][39][40]. And our study first illuminated that TRAF4 was involved in SCLC progression.…”

Section: Discussionmentioning

confidence: 53%

YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4

et al. 2020

View full text Add to dashboard Cite

Background: Newly identified lncRNA zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) is identified as an oncogenic gene. However, the role of ZFPM2-AS1 in small cell lung cancer (SCLC) is poorly comprehended. Methods: The expression of genes in SCLC tissues and cells was measured by qRT-PCR. Colony formation, EdU, CCK-8, transwell and wound healing as well as in vivo assays revealed the function of ZFPM2-AS1 in SCLC. ChIP, luciferase reporter, RIP and RNA pull down assays demonstrated the binding relation among genes. Results: ZFPM2-AS1 was significantly upregulated in SCLC tissues and cells. ZFPM2-AS1 deficiency attenuated SCLC cell proliferation, invasion and migration. In addition, ZFPM2-AS1 was transcriptionally activated by Yin Yang 1 (YY1) factor. Further, miR-3612 was confirmed as downstream miRNA of ZFPM2-AS1. Moreover, TNF receptor associated factor 4 (TRAF4) was the target gene of miR-3612 in SCLC. ZFPM2-AS1, miR-3612 and TRAF4 jointly constituted a competing endogenous RNA (ceRNA) network in SCLC. Finally, TRAF4 could countervail ZFPM2-AS1 downregulationmediated function on SCLC cell proliferation and invasion in vitro and tumor growth in vivo. Conclusion: Our study elucidated the oncogenic effect of ZFPM2-AS1 in SCLC progression, indicating it may be a therapeutic target for SCLC.

show abstract

“…TRAF2 regulates inflammatory cytokine production in tumor-associated macrophages, which facilitates tumor growth ( 46 ). TRAF4 promotes lung cancer aggressiveness by modulating the tumor microenvironment in normal fibroblasts via the TRAF4-NOX2/NOX4/p47-phox-ROS pathway ( 338 ). Importantly, TRAFs are also recognized as potential targets or modulators of cancer immunotherapy.…”

Section: Indirect Mechanisms Of Trafs In Human Cancersmentioning

confidence: 99%

Genetic Alterations of TRAF Proteins in Human Cancers

et al. 2018

View full text Add to dashboard Cite

The tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family of cytoplasmic adaptor proteins regulate the signal transduction pathways of a variety of receptors, including the TNF-R superfamily, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-I-like receptors (RLRs), and cytokine receptors. TRAF-dependent signaling pathways participate in a diverse array of important cellular processes, including the survival, proliferation, differentiation, and activation of different cell types. Many of these TRAF-dependent signaling pathways have been implicated in cancer pathogenesis. Here we analyze the current evidence of genetic alterations of TRAF molecules available from The Cancer Genome Atlas (TCGA) and the Catalog of Somatic Mutations in Cancer (COSMIC) as well as the published literature, including copy number variations and mutation landscape of TRAFs in various human cancers. Such analyses reveal that both gain- and loss-of-function genetic alterations of different TRAF proteins are commonly present in a number of human cancers. These include pancreatic cancer, meningioma, breast cancer, prostate cancer, lung cancer, liver cancer, head and neck cancer, stomach cancer, colon cancer, bladder cancer, uterine cancer, melanoma, sarcoma, and B cell malignancies, among others. Furthermore, we summarize the key in vivo and in vitro evidence that demonstrates the causal roles of genetic alterations of TRAF proteins in tumorigenesis within different cell types and organs. Taken together, the information presented in this review provides a rationale for the development of therapeutic strategies to manipulate TRAF proteins or TRAF-dependent signaling pathways in different human cancers by precision medicine.

show abstract

TRAF4 promotes lung cancer aggressiveness by modulating tumor microenvironment in normal fibroblasts

Cited by 34 publications

References 59 publications

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

ZFPM2-AS1 facilitates cell growth in esophageal squamous cell carcinoma via up-regulating TRAF4

YY1-induced lncRNA ZFPM2-AS1 facilitates cell proliferation and invasion in small cell lung cancer via upregulating of TRAF4

Genetic Alterations of TRAF Proteins in Human Cancers

Contact Info

Product

Resources

About