Upregulated lnc‐HZ02 and miR‐hz02 inhibited migration and invasion by downregulating the FAK/SRC/PI3K/AKT pathway in BPDE‐treated trophoblast cells

Guo, Jiarong; Li, Rui; Xu, Zhongyan; Tian, Peng; Wang, Rong; Li, Youzhu; Xia, Qi‐Dong; Zou, Peng; He, Mei; Ao, Lin; Liu, Qicai; Zhang, Huidong

doi:10.1002/jbt.22757

Cited by 20 publications

(7 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that HuR is an RNA binding protein, which could bind RNAs containing AUUU specific sequence and enhance their RNA stability. 44 Here, we explored whether HuR protein could promote PLD1 mRNA stability in human trophoblast cells. We found that in both Swan 71 and HTR-8/SVneo cells, those with overexpression of HuR had higher, whereas those with HuR knockdown had lower PLD1 mRNA and protein levels ( Figure 2L ; S5C–F).…”

Section: Resultsmentioning

confidence: 99%

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

Dai

Huang

et al. 2023

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

Background: Recurrent miscarriage (RM) affects 1%–3% of pregnancies. However, in almost 50% of cases, the cause is unknown. Increasing evidence have shown that benzo(a)pyrene [B(a)P], a representative of polycyclic aromatic hydrocarbons (PAHs), is correlated with miscarriage. However, the underlying mechanisms of B(a)P/benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE)-induced trophoblast cell dysfunctions and miscarriage remain largely unknown. Objective: The objective was to discover the role(s) of a novel lncRNA, lnc-HZ09 , in the regulation of BPDE-inhibited migration and invasion of trophoblast cells and the occurrence of miscarriage. Method: Human trophoblast cells were treated with 0, 0.25, 0.5, BPDE with or without corresponding lnc-HZ09 silencing or overexpression. Using these cells, we evaluated cell migration and invasion, the mRNA and protein levels of members of the PLD1/RAC1/CDC42 pathway, the regulatory roles of lnc-HZ09 in PLD1 transcription and mRNA stability, and lnc-HZ09 transcription and stability. Human villous tissues were collected from RM ( ) group and their matched healthy control (HC, ) group. We evaluated the levels of BPDE-DNA adducts, lnc-HZ09, and the mRNA and protein expression of members of the PLD1/RAC1/CDC42 pathway, and correlated their relative expression levels. We further constructed 0, 0.05 or B(a)P-induced mouse miscarriage model (each ), in which the mRNA and protein expression of members of the Pld1/Rac1/Cdc42 pathway were measured. Results: We identified a novel lnc-HZ09 . Human trophoblast cells treated with lnc-HZ09 exhibited less cell migration and invasion. In addition, the levels of this lncRNA were higher in villous tissues from women with recurrent miscarriage than those from healthy individuals. SP1-mediated PLD1 mRNA levels were lower, and HuR-mediated PLD1 mRNA stability was less in trophoblast cells overexpressing lnc-HZ09 . However, trophoblast cells treated with MSX1 had higher levels of lnc-HZ09 , and METTL3-mediated m6A methylation on lnc-HZ09 resulted in greater lnc-HZ09 RNA stability. In BPDE-treated human trophoblast cells and in RM villous tissues, MSX1-mediated lnc-HZ09 transcription and METTL3-mediated lnc-HZ09 stability were both greater. In our mouse miscarriage model, B(a)P-treated mice had lower mRNA and protein levels of members of the Pld1/Rac1/Cdc42 pathway. Discussion: These results suggest that in human trophoblast cells, BPDE exposure up-regulated lnc-HZ09 level, suppressed PLD1/RAC1/CDC42 pathway, and inhibited migration and invasion, prov...

show abstract

Section: Resultsmentioning

confidence: 99%

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

Dai

Huang

et al. 2023

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

show abstract

“…Focal adhesion kinases (FAKs) are a class of cytoplasmic non-receptor protein tyrosine kinases that belong to the protein tyrosine kinase (PTK) superfamily and are therefore also known as PTK II (32). FAKs can integrate signals from integrins, growth factors and mechanical stimuli to activate intracellular PI3K/Akt, Ras/MAPK and other signaling pathways to regulate cell growth (33)(34)(35). Numerous studies on the association of FAKs with different types of cancers have shown a close link between FAKs and the biological mechanisms that promote cancer development and progression (36).…”

Section: Discussionmentioning

confidence: 99%

Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer

et al. 2022

View full text Add to dashboard Cite

BackgroundRecently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated.MethodsWe examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset.ResultsGFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs.ConclusionsOur work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies.

show abstract

“…In our recent work, we have identified that inhibition in trophablast cell proliferation, migration/invasion or the increase in trophoblast cell apoptosis is associated with RM. [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ] However, whether other dysfunctions of human trophoblast cells might also induce miscarriage should be further explored.…”

Section: Introductionmentioning

confidence: 99%

“…[ 45 ] Recently, we have found that BPDE induced trophoblast apoptosis, ferroptosis, and pyroptosis, and also inhibited trophoblast migration/invasion and proliferation. [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 46 ] In animal studies, we found that BaP exposure induced miscarriage of pregnant mice. [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 46 ] However, it is still unclear whether BPDE might impair HR repair in human trophoblast cells and whether this impairment might further induce miscarriage.…”

Section: Introductionmentioning

confidence: 99%

“…[ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 46 ] In animal studies, we found that BaP exposure induced miscarriage of pregnant mice. [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 46 ] However, it is still unclear whether BPDE might impair HR repair in human trophoblast cells and whether this impairment might further induce miscarriage. Moreover, PAH exposure activates the expression of AhR (aryl hydrocarbon receptor).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage

Chen,

Mi,

Zhang

et al. 2024

Advanced Science

Self Cite

View full text Add to dashboard Cite

Human trophoblast cells are crucial for healthy pregnancy. However, whether the defective homologous recombination (HR) repair of dsDNA break (DSB) in trophoblast cells may induce miscarriage is completely unknown. Moreover, the abundance of BRCA1 (a crucial protein for HR repair), its recruitment to DSB foci, and its epigenetic regulatory mechanisms, are also fully unexplored. In this work, it is identified that a novel lnc‐HZ10, which is highly experssed in villous tissues of recurrent miscarriage (RM) vs their healthy control group, suppresses HR repair of DSB in trophoblast cell. Lnc‐HZ10 and AhR (aryl hydrocarbon receptor) form a positive feedback loop. AhR acts as a transcription factor to promote lnc‐HZ10 transcription. Meanwhile, lnc‐HZ10 also increases AhR levels by suppressing its CUL4B‐mediated ubiquitination degradation. Subsequently, AhR suppresses BRCA1 transcription; and lnc‐HZ10 (mainly 1‐447 nt) interacts with γ‐H2AX; and thus, impairs its interactions with BRCA1. BPDE exposure may trigger this loop to suppress HR repair in trophoblast cells, possibly inducing miscarriage. Knockdown of murine Ahr efficiently recovers HR repair in placental tissues and alleviates miscarriage in a mouse miscarriage model. Therefore, it is suggested that AhR/lnc‐HZ10/BRCA1 axis may be a promising target for alleviation of unexplained miscarriage.

show abstract

Upregulated lnc‐HZ02 and miR‐hz02 inhibited migration and invasion by downregulating the FAK/SRC/PI3K/AKT pathway in BPDE‐treated trophoblast cells

Cited by 20 publications

References 23 publications

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

BPDE, the Migration and Invasion of Human Trophoblast Cells, and Occurrence of Miscarriage in Humans: Roles of a Novel lncRNA-HZ09

Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer

Defective Homologous Recombination Repair By Up‐Regulating Lnc‐HZ10/Ahr Loop in Human Trophoblast Cells Induced Miscarriage

Contact Info

Product

Resources

About