BACKGROUND: Interstitial cystitis is a diagnosis of exclusion due to the complexity of its etiology and pathology, which is a chronic disease with an unknown etiology. To our knowledge, few studies were performed to identify predictive biomarkers for interstitial cystitis.
OBJECTIVE: This study aimed to identify and validate potential biomarkers for Interstitial Cystitis (IC).
METHODS: The interstitial cystitis datasets were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using the R package and were subjected to functional and pathway enrichment analysis. Key biomarkers of interstitial cystitis were identified by using Lasso regression analysis and the SVM-RFE algorithm. The diagnostic value of key biomarkers was validated in internal and external datasets, and pathways that relate to biomarkers of interstitial cystitis were screened. The ssGSEA was employed to identify the immune cells closely related to biomarkers. The expression of PLAC8 in patients with interstitial cystitis was detected by Immune-Histochemistry (IHC).
RESULTS: Sixteen differentially expressed genes associated with interstitial cystitis were identified, which were primarily linked to the biological process of the chemokine signaling pathway. PLAC8, identified as a biomarker for interstitial cystitis, was validated to express a significantly different between IC and normal bladder tissues. PLAC8-related pathways were analyzed, with a focus on NF-κB, TNF, Toll-like receptor, chemokine, IL-17, and JAK-STAT signaling pathways. PLAC8 was proved to be closely related to immune activations, which is similar to the pathogenesis of IC, which is a chronic dysregulated immune disease. Meanwhile, we also observed a higher level of PLAC8 in IC tissues.
CONCLUSIONS: PLAC8 has promising application prospects as a biomarker for interstitial cystitis diagnosis. These findings could aid in the diagnosis and treatment of interstitial cystitis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that begins or is diagnosed during pregnancy. Our study aimed to establish a correlation between proinflammatory and anti-inflammatory response in order to be able to develop treatment strategies and determine early diagnosis biomarkers in the sera of cases diagnosed with GDM. Moreover, we aimed to investigate interleukin (IL), placenta-specific gene 8 protein (PLAC8) and total antioxidant capacity (TAC) in patients with GDM.
METHODS: A total of 121 patients were included in the study. These were divided into four patient groups: pregnant and diagnosed with DM (P-GDM, n=30); pregnant and not diagnosed with DM (P-NGDM, n=32); non-pregnant diagnosed with DM (NP-DM, n=29) and non-pregnant and not diagnosed with DM (NPNDM, n=30). IL-10, IL-17A, IL-21, IL-33, PLAC8 and TAC determinations from patients were evaluated by ELISA (Enzyme-Linked ImmunoSorbent Assay) method.
RESULTS: IL-10 and IL-33 concentrations were found to be significantly higher in P-GDM and NP-DM patient groups compared to P-NGDM and NP-NDM groups (p<0.001). The PLAC8 level in the P-GDM patient group (20.38±5.37) was determined to be significantly higher than in the P-NGDM patient group (3.41±2.17, p<0.001). TAC in the P-NGDM and NP-NDM groups (12.42±2.31 vs. 12.96±3.78, p<0.001) was determined to be significantly higher than in the P-GDM and NP-DM groups (4.8±0.52 vs. 2.21±0.71, p<0.001).
CONCLUSIONS: The fact that the importance of PLAC8 level and TAC in the diagnosis and follow-up of GDM in pregnancy is demonstrated for the first time in this study shows that it is unique.

UNASSIGNED: PLAC8 has been identified in the progression of various cancers by inducing tumorigenesis, immune response, chemotherapy resistance and metastasis. Nevertheless, the precise biological function of PLAC8 in renal cancer remains unknown.
UNASSIGNED: We obtained the expression profile and associated clinical characteristics of patients diagnosed with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas database. The biological behavior of specific cell lines was detected using Cell Counting Kit-8 (CCK-8), colony formation, and 5-ethynyl-2\'-deoxyuridine (EdU) assay. A prognostic model was constructed based on PLAC8-related molecules through a machine-learning algorithm.
UNASSIGNED: We observed overexpression of PLAC8 in ccRCC patients. In addition, PLAC8 has been identified as being linked to unfavorable clinical characteristics and adverse prognosis outcomes. Biological enrichment analysis revealed the potential involvement of PLAC8 in cell cycle checkpoints, mitotic phase transformation, immunotherapy-predicted and reactive oxygen species (ROS) related pathways. In addition, immune analyses showed that PLAC8 was involved in remodeling the tumor microenvironment (TME) and affecting the effect of immunotherapy in ccRCC patients. In vitro experiments demonstrated a significant reduction in the proliferation, invasion and migration of renal cancer cells following the knockdown of PLAC8. Finally, LASSO logistics regression was applied to construct a prognosis model, which presented a favorable prediction ability on the prognosis of ccRCC.
UNASSIGNED: Our results implied that PLAC8 may be a novel immunotherapy biomarker of ccRCC, which is a crucial molecule in remodeling the cancer microenvironment. PLAC8 can predict immunotherapy response and is expected to guide precise treatment.

UNASSIGNED: Pancreatic cancer is a highly aggressive and lethal disease with limited treatment options. In this study, we investigated the potential therapeutic effects of compound KL-6 on pancreatic cancer cells.
UNASSIGNED: The study involved assessing the inhibitory effects of KL-6 on cell proliferation, clonogenic potential, cell cycle progression, apoptosis, migration, and invasion. Additionally, we examined the action mechanism of KL-6 by RNA-seq and bioinformatic analysis and validated by qRT-PCR and western blot in pancreatic cancer cells.
UNASSIGNED: Our results demonstrated that KL-6 effectively inhibited the growth of pancreatic cancer cells in a dose-dependent manner. It induced G2/M phase cell cycle arrest and apoptosis, disrupting the cell cycle progression and promoting cell death. KL-6 also exhibited inhibitory effects on cell migration and invasion, suggesting its potential to suppress the metastatic properties of pancreatic cancer cells. Furthermore, KL-6 modulated the expression of genes involved in various cancer-related pathways including apoptosis and ferroptosis.
UNASSIGNED: These findings collectively support the potential of KL-6 as a promising therapeutic option for pancreatic cancer treatment. Further research is needed to fully understand the underlying mechanisms and evaluate the clinical efficacy of KL-6 in pancreatic cancer patients.

BACKGROUND: The main symptoms of preeclampsia (PE), a specific ailment that develops during pregnancy, are proteinuria and hypertension. The pathological root of the onset and progression of PE is widely regarded as abnormal placental trophoblast cell function. This study aimed to look into the character and mechanism of Placenta-specific 8 (PLAC8) in trophoblast cell invasion and migration.
METHODS: Expressions of PLAC8 and AlkB homologue 5 (ALKBH5) were examined by western blot and quantitative real-time PCR. The m6A level of PLAC8 mRNA was detected by methylated RNA Immunoprecipitation. Using Transwell experiments, cell invasion and migration were examined. The enzyme-linked immunosorbent assay was utilized to analyze the MMP-2 and MMP-9 secretion levels. RNA pull-down and RNA immunoprecipitation were conducted to detect the binding between ALKBH5 and PLAC8.
RESULTS: In PE tissue and hypoxia-treated HTR-8/SVneo cells, levels of ALKBH5 and PLAC8 were increased, and PLAC8 m6A methylation levels were decreased. There was a positive correlation between PLAC8 and ALKBH5 expression in clinical tissues. In addition, overexpressing PLAC8 promoted HTR-8/SVneo cell migration and invasion, and so as the levels of MMP-2 and MMP-9; while interference with PLAC8 reduced the migration and invasion of hypoxia-treated HTR-8/SVneo cells, and so as the levels of MMP-2 and MMP-9. Moreover, the PLAC8 mRNA\'s m6A modification site was GAACU (Position 1449, Site 2). Increased levels of MMP-2 and MMP-9, as well as migration and invasion of HTR-8/SVneo cells exposed to hypoxia, were all facilitated by the m6A Site2 mutation. Furthermore, ALKBH5 could bind to PLAC8, reduce its m6A modification, and promote its expression.
CONCLUSIONS: High-expressed ALKBH5 inhibits the m6A level of PLAC8 mRNA and promotes PLAC8 expression, while PLAC8 overexpression can promote hypoxia-induced invasion and migration of HTR-8/Svneo cells, indicating its potential protective function in PE.

Cadmium (Cd) pollution of soil occurs worldwide. Phytoremediation is an effective approach for cleaning up Cd polluted soil. Fast growing Populus species with high Cd uptake capacities are desirable for phytoremediation. Thus, it is important to elucidate the molecular functions of genes involved in Cd uptake by poplars. In this study, PcPLAC8-10, a homolog of Human placenta-specific gene 8 (PLAC8) implicated in Cd transport was functionally characterized in Populus × canescens. PcPLAC8-10 was transcriptionally induced in Cd-treated roots and it encoded a plasma membrane-localized transporter. PcPLAC8-10 exhibited Cd uptake activity when expressed in yeast cells. No difference in growth was observed between wild type (WT) and PcPLAC8-10-overexpressing poplars. PcPLAC8-10-overexpressing poplars exhibited increases in net Cd2+ influxes by 192% and Cd accumulation by 57% in the roots. However, similar reductions in biomass were found in WT and transgenic poplars when exposed to Cd. The complete motif of CCXXXXCPC in PcPLAC8-10 was essential for its Cd transport activity. These results suggest that PcPLAC8-10 is a plasma membrane-localized transporter responsible for Cd uptake in the roots and the complete CCXXXXCPC motif of PcPLAC8-10 plays a key role in its Cd transport activity in poplars.

DExD/H-box helicase (DDX) 5 belongs to the DExD/H-box helicase family. DDX family members play differential roles in the regulation of innate antiviral immune response. However, whether DDX5 is involved in antiviral immunity remains unclear. In this study, we found that DDX5 serves as a negative regulator of type I interferon (IFN) response. Overexpression of DDX5 inhibited IFN production induced by Spring viremia of carp virus (SVCV) and poly(I:C) and enhanced virus replication by targeting key elements of the RLR signaling pathway (MAVS, MITA, TBK1, IRF3 and IRF7). Mechanistically, DDX5 directly interacted with TBK1 to promote its autophagy-mediated degradation. Moreover, DDX5 was shown to block the interaction between TRAF3 and TBK1, hence preventing nuclear translocation of IRF3. Together, these data shed light on the roles of DDX5 in regulating IFN response.

Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial-mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKTSer473 and p-AKTThr308 expression after PLAC8 knockdown. Furthermore, PLAC8 overexpression upregulated the expression of sex-determining region Y-related high-mobility group box transcription factor 4 (SOX4), which is reported to mediate the activation of the AKT pathway, and SOX4 deficiency reversed the cellular functions caused by PLAC8 overexpression. Overall, the present study indicates that PLAC8 may facilitate CC development by activating the SOX4-mediated AKT pathway, suggesting that PLAC8 may serve as a potential biomarker for CC treatment.

Triple-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.
We 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.
PLAC8 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.
Our 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.

Better understanding on interactions between SARS-CoV-2 and host cells should help to identify host factors that may be targetable to combat infection and COVID-19 pathology. To this end, we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate many findings from previous screens that used full SARS-CoV-2 viruses, but also unveil two novel critical host factors: the lysosomal efflux transporter SPNS1 and the plasma and lysosomal membrane protein PLAC8. Functional experiments with full SARS-CoV-2 viruses confirm that loss-of-function of these genes impairs viral entry. We find that PLAC8 is a key limiting host factor, whose overexpression boosts viral infection in eight different human lung cancer cell lines. Using single-cell RNA-Seq data analyses, we demonstrate that PLAC8 is highly expressed in ciliated and secretory cells of the respiratory tract, as well as in gut enterocytes, cell types that are highly susceptible to SARS-CoV-2 infection. Proteomics and cell biology studies suggest that PLAC8 and SPNS1 regulate the autophagolysosomal compartment and affect the intracellular fate of endocytosed virions.