Novel lnc-HZ03 and miR-hz03 promote BPDE-induced human trophoblastic cell apoptosis and induce miscarriage by upregulating p53/SAT1 pathway

Novel lncRNA‐HZ04 promotes BPDE‐induced human trophoblast cell apoptosis and miscarriage by upregulating IP3R1/CaMKII/SGCB pathway by competitively binding with miR‐hz04

“…This loop is upregulated in both RM tissues and BPDE‐exposed trophoblast cells, which further promotes EIF4E transcription, inhibits trophoblast cell proliferation, and induces miscarriage. We also found that, in BPDE‐exposed human trophoblast cells and in RM tissues, lnc‐HZ03 and miR‐hz03 upregulates p53/SAT1 axis and promote spermine metabolism, which further promote BPDE‐induced human trophoblastic cell apoptosis and the occurrence of miscarriage 21 . Recently, we have found that lnc‐HZ08 regulates BPDE‐induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is also associated with miscarriage 38 .…”

“…Fifteen women who had undergone artificial miscarriages to terminate unwanted pregnancies (the HC group) and 15 patients with two or more consecutive unexplained miscarriage (the RM group) in the age between 25 and 30 were recruited, as described previously. 21,37,38 All HC groups have previous pregnancies. Any woman with one of the following features was excluded, including autoimmune abnormality, luteal phase defects, hyperprolactinemia, antiphospholipid antibody syndrome, or hyperandrogenemia; uterine abnormalities or cervical incompetence; abnormal karyotype of the parents or abortus; polycystic ovarian syndrome; the symptoms of endocrine or metabolic diseases; viral infectious diseases; tuberculosis, HBV, HCV, HIV, or with positive results from γ-interferon release tests; and eclampsia or preeclampsia.…”

“…2.9 | Quantitative real-time polymerase chain reaction RT-qPCR analysis was performed as described previously. 21,37,38 Total RNAs were extracted from cells or tissues. Subsequently, mRNA and lncRNA were reversely transcribed into cDNA using the Prime Script RT Reagent Kit with gDNA Eraser (Takara).…”

“…The methods were similar to those described previously. 21,37,38 The primary antibodies contained anti-IP 3 R 1 (dilution 1:1000, ab264281, Abcam, Cambridge, UK), anti-CaMKII (dilution 1:1000, 4436S, Cell Signaling Technology, Boston, USA), anti-p-CaMKII (dilution 1:1000, 3356S, Cell Signaling Technology), anti-SGCB (dilution 1:100, sc-5306, SANTA Cruz, Texas, USA), anti-p53 (ab1101, Abcam), and anti-GAPDH (dilution 1:10 000, ab8245, Abcam). The secondary antibodies included goat anti-rabbit IgG (dilution 1:5000, ab205718, Abcam) and goat anti-mouse IgG (dilution 1:5000, ab205719, Abcam).…”

“…Recently, we have found that BPDE could induce the apoptosis of human extravillous trophoblast Swan 71 cells due to the disorders of mitochondrial fission/fusion 20 or due to the upregulation of SAT1-mediated spermine metabolism. 21 Intracellular Ca 2+ plays important roles in the regulation of a variety of cellular processes, such as cell cycle, apoptosis, and migration. 22,23 Recent studies have shown that inositol trisphosphate receptor type 1 (IP 3 R 1 )-mediated Ca 2+ release upregulates the cytosolic-free Ca 2+ level, which induces rat miscarriage.…”