Ask about this productRelated genes to: C12ORF49 Blocking Peptide
- Gene:
- C12orf49 NIH gene
- Name:
- chromosome 12 open reading frame 49
- Previous symbol:
- -
- Synonyms:
- FLJ21415
- Chromosome:
- 12q24.22
- Locus Type:
- gene with protein product
- Date approved:
- 2006-01-24
- Date modifiied:
- 2016-09-30
Related products to: C12ORF49 Blocking Peptide
Related articles to: C12ORF49 Blocking Peptide
- Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for novel therapeutic strategies. Recent studies have highlighted the pivotal role of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, in cancer biology. C12ORF49, an emerging regulator of lipid metabolism, has gained attention for its influence on HCC cell survival and tumor progression. Specifically, C12ORF49 modulates the SREBP1/SCD1-mediated fatty acid metabolic pathway, which in turn suppresses ferroptosis, facilitating tumor cell survival and resistance to conventional therapies. Despite advances in understanding ferroptosis pathways, the complex interplay between lipid metabolism regulators like C12ORF49 and ferroptotic signaling in HCC remains incompletely understood. This review comprehensively summarizes current knowledge on the molecular mechanisms by which C12ORF49 intersects with ferroptosis signaling, highlighting its impact on lipid metabolic reprogramming in HCC. Furthermore, we explore the potential of targeting C12ORF49 to enhance the efficacy of existing treatments such as Sorafenib, a frontline systemic therapy for advanced HCC. By elucidating the crosstalk between C12ORF49 and ferroptosis pathways, this article aims to provide a theoretical framework and identify promising therapeutic targets for precision medicine approaches in hepatocellular carcinoma. - Source: PubMed
Publication date: 2026/02/09
Liu YuexinJia LizhouYang LiuNing ZhangLi Yanmei - Hepatocellular carcinoma (HCC) is a common and serious type of malignant tumor with an unfavorable prognosis, partly attributed to the prevalence of hepatitis B virus (HBV) infection. However, the molecular mechanism underlying HBV-HCC are not yet fully understood. Here, we found that Kruppel-like factor 16 (KLF16) was significantly upregulated in HBV-HCC and KLF16 knockdown suppressed the growth and metastasis of HBV-infected HCC cells. Hepatitis B virus X protein (HBx)-mediated N6-methyladenosine (m6A) modification of KLF16 mRNA promoted the binding of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and IGF2BP3, thereby enhancing the stability of KLF16 mRNA. Furthermore, KLF16 was found to promote the transcription of chromosome 12 open reading frame 49 (C12orf49), which in turn increased programmed death-ligand 1 (PD-L1) expression by competitively binding to speckle-type POZ protein (SPOP) and blocking SPOP-mediated ubiquitination and degradation of PD-L1. HBx contributed to immune escape in HBV-HCC through the KLF16-C12orf49-PD-L1 axis. Importantly, inhibiting KLF16 significantly improved the efficacy of anti-PD-L1 therapy in HBV-HCC. Collectively, our study reveals the newly identified HBx-KLF16-C12orf49-PD-L1 axis and its role in promoting growth and immune evasion in HBV-HCC, offering a promising target for clinical interventions in HBV-HCC treatment. - Source: PubMed
Publication date: 2025/11/14
Chen WenbiaoLin ChenhongWang LuolinYu ZhichaoXu YuxiuxiuZhang MinhaiWang LishengYao Jun - Lipid metabolism and de-novo lipogenesis (DNL) is broadly controlled by the SREBP transcription factors. These transcription factors are matured from membrane-anchored precursor proteins by the proteolytic actions of the proteases S1P and S2P. In this review, we summarize the current understanding of SPRING, a recently identified activator of S1P. - Source: PubMed
Publication date: 2025/08/01
Micallo IlariaBullington Ashley VKober Daniel LZelcer Noam - Altered lipid metabolism is an emerging hallmark of cancer, which is involved in various aspects of the cancer phenotypes. C12ORF49 has recently been identified as a pivotal regulator of sterol regulatory element binding proteins (SREBPs), a family of transcriptional factors that govern lipid biosynthesis. Nevertheless, the function of C12ORF49 in human cancers has not been studied. Here, we show that C12ORF49 levels are higher in HCC tissue than in nearby non-cancerous liver tissue. Additionally, increased C12ORF49 expression is linked to poorer survival outcomes in HCC patients. Functional experiments uncovered that knockdown of C12ORF49 inhibited HCC cell survival and tumor growth by inducing ferroptosis, whereas the opposites were observed upon C12ORF49 overexpression. Mechanistically, C12ORF49 promotes SREBP1/SCD-regulated production of monounsaturated fatty acids, which inhibits ferroptosis in HCC cells. Furthermore, silencing C12ORF49 combined with Sorafenib treatment showed a synergistic effect in inducing HCC cell death. Together, our findings suggest a critical role of C12ORF49 in the evasion of ferroptosis in HCC cells, highlighting the potential of targeting C12ORF49 as a therapeutic strategy to enhance the efficacy of Sorafenib treatment in HCC. - Source: PubMed
Publication date: 2025/04/16
Yu Heng-ChaoJin LiangBai LuZhang Yu-JiaYang Zhao-Xu - SREBP transcription factors are central regulators of lipid metabolism. Their proteolytic activation requires ER to the Golgi translocation and subsequent cleavage by site-1-protease (S1P). Produced as a proprotein, S1P undergoes autocatalytic cleavage from its precursor S1P to mature S1P form. Here, we report that SPRING (previously C12ORF29) and S1P interact through their ectodomains, and that this facilitates the autocatalytic cleavage of S1P into its mature S1P form. Reciprocally, we identified a S1P recognition-motif in SPRING and demonstrate that S1P-mediated cleavage leads to secretion of the SPRING ectodomain in cells, and in liver-specific knockout (LKO) mice transduced with AAV-mSpring. By reconstituting SPRING variants into SPRING cells we show that the SPRING ectodomain supports proteolytic maturation of S1P and SREBP signaling, but that S1P-mediated SPRING cleavage is not essential for these processes. Absence of SPRING modestly diminishes proteolytic maturation of S1P and trafficking of S1P to the Golgi. However, despite reaching the Golgi in SPRING cells, S1P fails to rescue SREBP signaling. Remarkably, whereas SREBP signaling was severely attenuated in SPRING cells and LKO mice, that of ATF6, another S1P substrate, was unaffected in these models. Collectively, our study positions SPRING as a dedicated licensing factor for SREBP-specific activation by S1P. - Source: PubMed
Publication date: 2024/05/15
Hendrix SebastianTan Josephine M ENdoj KlevisKingma JeninaValiloo MasoudZijlstra Lobke FOttenhoff RoelofSeidah Nabil GLoregger AnkeKober Daniel LZelcer Noam