Multifaced roles of PLAC8 in cancer

Mao, Misha; Cheng, Yifan; Yang, Jingjing; Chen, Yongxia; Xu, Ling; Zhang, Xun; Li, Zhaoqing; Chen, Cong; Ju, Siwei; Zhou, Jichun; Wang, Linbo

doi:10.1186/s40364-021-00329-1

Cited by 22 publications

(20 citation statements)

References 111 publications

(172 reference statements)

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“…PLAC8 is reported to be involved in the cancer immune response, 11 so we further tested whether there is a connection between PLAC8 and the immune response in TNBC. As shown in figure 4A, B , knockdown of PLAC8 induced the secretion of interleukin-2 (IL-2) by Jurkat cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous research suggested that PLAC8 can promote breast cancer cell growth and participate in the process of tamoxifen and adriamycin resistance. 8–10 As we mentioned in our review, 11 PLAC8 also plays an important role in various cancers and is involved in tumor progression, including in programmed cell death, cancer stemness and cancer immunity. This finding indicates that PLAC8 has important clinical significance in breast cancer.…”

Section: Introductionmentioning

confidence: 90%

“…PLAC8 is reported to be involved in the cancer immune response, 11 so we further tested whether there is a connection between PLAC8 and the immune response in TNBC.…”

Section: Plac8 Interacts With Glycosylated and Ubiquitinated Pd-l1mentioning

confidence: 99%

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Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer

Mao

Chen

Yang

et al. 2022

J Immunother Cancer

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BackgroundTriple-negative breast cancer is characterized by a poor prognosis and lack of targeted treatments, and thus, new targeting markers and therapeutic strategies are urgently needed. We previously indicated that PLAC8 promotes tumorigenesis and exerts multidrug resistance in breast cancer. Therefore, we aimed to characterize the PLAC8-regulated network in triple-negative breast cancer.MethodsWe measured the levels of PLAC8 in breast cancer cell lines and found that PLAC8 is post-translationally modified by ubiquitin-fold modifier 1 (UFM1). Then, we revealed a new regulatory system of PD-L1 by PLAC8 in triple-negative breast cancer. We also tested the molecular functions of PLAC8 in triple-negative breast cancer cell lines and measured the expression of PLAC8 and PD-L1 in breast cancer tissues.ResultsPLAC8 was generally highly expressed in triple-negative breast cancer and could be modified by UFM1, which maintains PLAC8 protein stability. Moreover, PLAC8 could promote cancer cell proliferation and affect the immune response by regulating the level of PD-L1 ubiquitination. Additionally, among patients with breast cancer, the expression of PLAC8 was higher in triple-negative breast cancer than in non-triple-negative breast cancer and positively correlated with the level of PD-L1.ConclusionsOur current study discoveries a new PLAC8-regulated network in triple-negative breast cancer and provides corresponding guidance for the clinical diagnosis and immunotherapy of triple-negative breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

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Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer

Mao

Chen

Yang

et al. 2022

J Immunother Cancer

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“…But we also nd DEGs in our myleloid cell types with unknown association to MD such as placenta-speci c gene 8-like 2 (PLAC8). Of note, PLAC8 research suggests a multifaceted role in tumorigenesis 53 , but its contribution in MD is unknown. Macrophages represent another fundamental means to diminish viral infection 12 54 and a RNAseq analysis of in vitro MDV-infected macrophages showed signi cant gene expression changes in resistant birds 12 .…”

Section: Discussionmentioning

confidence: 99%

The immune cell landscape and response of Marek’s disease resistant and susceptible chickens infected with Marek’s disease virus

Warren

Rice

Meyer

et al. 2022

Preprint

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Genetically resistant or susceptible chickens to Marek’s disease (MD) have been widely used models to identify the molecular determinants of these phenotypes. However, these prior studies lacked the basic identification and understanding of immune cell types that could be translated toward improved MD control. To gain insights into specific immune cell types and their responses to Marek’s disease virus (MDV) infection, we used single-cell RNA sequencing (scRNAseq) on splenic cells from MD resistant and susceptible birds. Totally, 14,378 cells formed clusters that identified various immune cell types. Lymphocytes, specifically T cell subtypes, were the most abundant with significant proportional changes in some subtypes upon infection. The largest number of differentially expressed genes (DEG) response was seen in granulocytes, while macrophage DEGs differed in directionality by subtype and line. Among the most DEG in almost all immune cell types were granzyme and granulysin, both associated with cell-perforating processes. Protein interactive network analyses revealed multiple overlapping canonical pathways within both lymphoid and myeloid cell lineages. This initial estimation of the chicken immune cell type landscape and its accompanying response will greatly aid efforts in identifying specific cell types and improving our knowledge of host response to viral infection.

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“…Placenta-associated 8 protein (PLAC8), which was identified as a placentaregulatory gene, is highly expressed in mid-gestation placentas, intestine and endometrium [6] . Since PLAC8 was identified, many studies have demonstrated that it played a key role in regulating cell immunity [7] , sepsis [8] , autophagy [9] , and DNA repair [10] , and it actively participated in the control of various human cancers, acting as an oncogenic or tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

PLAC8 facilitates osteosarcoma growth and metastasis by upregulating CXCL5 expression via miR-363-3p

Huang

Zhang

et al. 2023

Preprint

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Background: Osteosarcoma (OS) is characterized by its highly aggressive nature and metastatic potential. Although dysregulated PLAC8 was reported in various cancers, its function and underlying mechanism in OS metastasis remains largely unknown. Methods: The expression of PLAC8 was detected by qRT-PCR and Western blot in OS clinical tissues and OS cell lines. CCK-8, colony formation, transwell and wound healing assays were performed to assess its effect on tumor cell proliferation and mobility. The relationship between PLAC8 and CXCL5 expression was analyzed by TIMER 2.0 database, qRT-PCR, Western blot and immunohistochemical staining. The qRT-PCR, Western blot, and luciferase reporter assays were performed to explore molecular mechanisms through which PLAC8 mediates the expression of miR-363-3p, thus modulating the expression of CXCL5.Subcutaneous transplantation, orthotopic tibia implantation, and tail-vein injection mouse model were employed to evaluate the role of PLAC8 on OS tumor growth and lung metastasis. Results: We found PLAC8 was upregulated in OS tissues and OS cell lines, and its overexpression facilitated the aggressive progression of OS. Besides, we identified CXCL5, as a downstream target gene of PLAC8, could potentiate OS cell proliferation, migration, and invasion. Mechanistically, PLAC8 down-regulated the levels of miR-363-3p which directly targeted CXCL5 3'-UTR, thus enhancing the proliferative and metastatic potency of OS cells. In subcutaneous transplantation and orthotopic tibia implantation mouse model, down-regulation of PLAC8 could markedly attenuate the OS tumorigenesis. In tail-vein injection mouse model, knockdown of PLAC8 could prominently restrain the OS lung metastasis. Moreover, we found that rhCXCL5 and miR-363-3p inhibitors significantly reversed the suppressive effect of PLAC8 silencing on OS growth and lung metastasis in vivo. Conclusions: PLAC8 is highly expressed in OS, which especially contributes to tumor growth and metastasis by regulating the miR-363-3p/CXCL5 axis. This study suggested that PLAC8 may serve as a promoter in OS and provided new insight into the treatment of OS lung metastasis.

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Multifaced roles of PLAC8 in cancer

Cited by 22 publications

References 111 publications

Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer

Modification of PLAC8 by UFM1 affects tumorous proliferation and immune response by impacting PD-L1 levels in triple-negative breast cancer

The immune cell landscape and response of Marek’s disease resistant and susceptible chickens infected with Marek’s disease virus

PLAC8 facilitates osteosarcoma growth and metastasis by upregulating CXCL5 expression via miR-363-3p

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