Tumor Suppressor LINC02487 Inhibits the Progression of Cervical Cancer in Vitro by Regulating the PTEN/Akt/mTOR Pathway.

OBJECTIVE: Cervical cancer (CC) ranks among the most prevalent malignant tumors affecting the female reproductive system. Nonetheless, various shortcomings exist within current treatment approaches for CC. Therefore, the quest for new intervention targets holds significant importance. Research has demonstrated that long non-coding RNA (lncRNA) long intergenic non-protein coding RNA 2487 (LINC02487) can suppress the development of oral squamous cell carcinoma (OSCC). However, its function and potential mechanisms in CC remain unclear, therefore, this study aims to investigate the role and potential mechanism of LINC02487 in CC. METHODS: LINC02487 and phosphatase and tensin homolog (PTEN) expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) in CC tissue samples and constructed cell models. LINC02487 was either knocked down or overexpressed, and PTEN was knocked down in the CC (SiHa) cell line via transfection technology. The expression levels of LINC02487 and PTEN in SiHa cell lines were examined using RT-qPCR after various treatments. Cell proliferation ability was determined through Cell Counting Kit (CCK)-8 and colony formation assays, while the ability to invade and migrate was assessed via Transwell experiments. Western blot analysis was employed to measure the levels of key proteins in the PTEN/Akt/mechanistic target of the rapamycin (mTOR) signaling pathway. RESULTS: A positive correlation was observed between LINC02487 and PTEN, both of which were found to be downregulated in CC cells and tissues (p < 0.05). In vitro experiments demonstrated that overexpression of LINC02487 significantly inhibited colony formation (p < 0.01), invasion (p < 0.01), migration (p < 0.01), and proliferation (p < 0.01) of SiHa cells. Furthermore, LINC02487 overexpression led to upregulation of PTEN expression (p < 0.01) and inhibition of the Akt/mTOR signaling pathway (p < 0.01), while knockdown of LINC02487 produced the opposite effect (p < 0.01). Additionally, knocking down PTEN counteracted the inhibitory effects of LINC02487 overexpression on CC progression (p < 0.01) and the Akt/mTOR signaling pathway (p < 0.01). CONCLUSION: In vitro findings suggest that LINC02487 may impede the progression of CC by suppressing the Akt/mTOR signaling pathway through the upregulation of PTEN expression. Consequently, LINC02487 holds promise as a potential therapeutic target for the treatment of CC.

ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

CELSR1 variants are associated with partial epilepsy of childhood.

CELSR1 gene, encoding cadherin EGF LAG seven-pass G-type receptor 1, is mainly expressed in neural stem cells during the embryonic period. It plays an important role in neurodevelopment. However, the relationship between CELSR1 and disease of the central nervous system has not been defined. In this study, we performed trios-based whole-exome sequencing in a cohort of 356 unrelated cases with partial epilepsy without acquired causes and identified CELSR1 variants in six unrelated cases. The variants included one de novo heterozygous nonsense variant, one de novo heterozygous missense variant, and four compound heterozygous missense variants that had one variant was located in the extracellular region and the other in the cytoplasm. The patients with biallelic variants presented severe epileptic phenotypes, whereas those with heterozygous variants were associated with a mild epileptic phenotype of benign epilepsy with centrotemporal spikes (BECTS). These variants had no or low allele frequency in the gnomAD database. The frequencies of the CELSR1 variants in this cohort were significantly higher than those in the control populations. The evidence from ClinGen Clinical-Validity Framework suggested a strong association between CELSR1 variants and epilepsy. These findings provide evidence that CELSR1 is potentially a candidate pathogenic gene of partial epilepsy of childhood.

ent-Abietane and ent-kaurane diterpenoids from the roots of Suregada glomerulata.

Twelve ENT-abietane and ENT-kaurane type diterpenoids, 1- 12, including five new compounds 1- 5, were isolated from the roots of Suregada glomerulata. The structures of the new compounds were elucidated on the basis of 1D and 2D NMR and other spectroscopic studies, and the structures of 1 and 2 were confirmed by X-ray crystallography. Cytotoxic activities against five human tumor cell lines were evaluated.