A Bivariate Twin Study of Cortical Surface Area and Verbal and Nonverbal Intellectual Skills in Adolescence.

Understanding the biological basis of cognitive differences between individuals is the goal in human intelligence research. The surface area of the cortex is considered to be a key determinant of human intelligence. Adolescence is a period of development characterized by physiological, emotional, behavioral, and psychosocial changes, which is related to the recombination and optimization of the cerebral cortex, and cognitive ability changes significantly in children and adolescents. This study examined the effects of common genetic and environmental factors between the surface area of the cerebral cortex and intelligence in typical developing adolescents (twins, n = 114, age 12-18 years old). Cortical surface area data were parsed into subregions (i.e., frontal, parietal, occipital, and temporal areas) and intelligence into verbal and nonverbal skills. We found a phenotypic correlation between regional surface areas and verbal intelligence. No correlation was observed between regional surface areas and nonverbal intelligence, except for the occipital lobe and the right hemisphere. In the bivariate twin analyses, the differences in phenotypic correlation between regional surface areas and verbal intelligence were not due to unshared environmental effects or measurement error, but to genetic effects. In summary, the current study has broadened the previous genetic investigations of cognitive ability and cortical surface area.

Case report: Long response to PD-1 blockade after failure of trastuzumab plus chemotherapy in advanced Epstein-Barr virus-associated gastric cancer.

Background: Trastuzumab-containing chemotherapy is the first-line treatment for advanced gastric cancer (GC) with HER2 positive. Although PD-1 inhibitors significantly improved the outcome of GC patient's refractory to previous chemotherapy regimens, few studies explore the role of anti-PD-1 therapy overcomes resistance to trastuzumab plus chemotherapy in advanced Epstein-Barr Virus-associated gastric cancer (EBVaGC) with PD-L1 and HER2 positive. Case Presentation: We report a case of advanced EBVaGC in a 45-year-old man presenting with fatigue, dysphagia, and weight loss for several months. Initial endoscopy revealed a large tumor at the gastroesophageal junction. Computed tomography revealed GC accompanied by multiple lymph nodes and hepatic and pulmonary metastases. The immunohistochemistry indicated that HER-2 and PD-L1 were overexpressed, and tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. Trastuzumab plus DCS was started as first-line chemotherapy with a PFS of 4 months and shifted to trastuzumab plus FOLFIRI or gemcitabine as second-/third-line therapy. After five-cycle nivolumab monotherapy, the patient received partial response and was treated with total radical gastrectomy plus sequential radiotherapy. He continued the postoperative immunotherapy over 30 cycles with a PFS of 28 months. Due to a new abdominal lymph node metastasis confirmed by PET-CT, he received toripalimab as the next-line treatment and achieved complete remission as the best objective response. Summary: We presented an advanced HER2-positive EBVaGC patient with PD-L1 high expression, refractory to trastuzumab plus chemotherapy, and had a durable clinical benefit sequence with a single dose of the PD-1 inhibitor.

Hsa_circ_0060937 accelerates non-small cell lung cancer progression via modulating miR-195-5p/HMGB3 pathway.

Circular RNAs (circRNAs) exert a critical effect on tumorigenesis and development. Our research aimed to clarify the function and underlying mechanism of circ_0060937 inNSCLC. The concentrations of circ_0060937, miR-195-5p and high-mobility group box 3 (HMGB3) were monitored via qRT-PCR and western blot assays. Additionally, cell proliferation, apoptosis, migration and invasion were assessed using CCK-8, colony formation, flow cytometry and transwell assays. Glycolysis was evaluated via detecting glucose uptake and lactate product. The association between miR-195-5p and circ_0060937/HMGB3 were validated using dual-luciferase reporter, RNA pull-down and RIP assays. Furthermore,in vivo experiment was performed to analyze tumorigenesis.Circ_0060937 and HMGB3 levels were elevated, whereas miR-195-5p level was dropped in NSCLC. Circ_0060937 down-regulation restrainedNSCLC cell proliferation, migration, invasion and glycolysis, and triggered apoptosis. Knockdown of circ_0060937 restrained NSCLC development via absorbing miR-195-5p. Circ_0060937 silencing inhibited NSCLC progression by mediating HMGB3. Besides, circ_0060937 depletion suppressed tumor growth in vivo.Circ_0060937 knockdown hindered NSCLC development and glycolysis via regulating miR-195-5p/HMGB3 pathway.

Circular RNA Circ_0016760 Modulates Non-Small-Cell Lung Cancer Growth Through the miR-577/ZBTB7A Axis.

BACKGROUND: Patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) have a poor prognosis. Circular RNA circ_0016760 (circ_0016760) is associated with the development of NSCLC. At present, the role and regulatory mechanism of circ_0016760 in NSCLC have not been well explained. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of circ_0016760, miR-577, and Zinc finger and BTB domain containing 7A (ZBTB7A) mRNA in NSCLC tissues and cells. The colony formation, migration, invasion, and extracellular acidification rate (ECAR) of NSCLC cells were determined through colony formation, transwell, or ECAR assays. The relationship between circ_0016760 or ZBTB7A and miR-577 was analyzed via dual-luciferase reporter and RNA pull-down or RNA immunoprecipitation (RIP) assays. Protein level of ZBTB7A was evaluated with Western blot analysis. Xenograft assay was conducted to confirm the role of circ_0016760 in vivo. RESULTS: Circ_0016760 and ZBTB7A were upregulated and miR-577 was downregulated in NSCLC tissues and cells. Circ_0016760 exhaustion curbed the colony formation, migration, invasion, and ECAR of NSCLC cells in vitro and impeded tumor growth in vivo. Mechanically, circ_0016760 modulated ZBTB7A expression via sponging miR-577 in NSCLC cells. MiR-577 downregulation abolished the repressive effects of circ_0016760 silencing on colony formation, migration, invasion, and ECAR of NSCLC cells. Also, ZBTB7A upregulation overturned the repressive impacts of miR-577 elevation on colony formation, migration, invasion, and ECAR of NSCLC cells. CONCLUSION: Circ_0016760 silencing impeded NSCLC advancement through regulation of the miR-577/ZBTB7A axis.

Attenuation of deregulated miR-369-3p expression sensitizes non-small cell lung cancer cells to cisplatin via modulation of the nucleotide sugar transporter SLC35F5.

Deregulation of the microRNAs (miRNAs), a cluster of important posttranscriptional regulators, has been frequently associated with lung cancer (LCa). However, the emerging mechanism for how miRNAs is linked causally in the development of LCa chemoresistance is poorly understood. Herein, we established for the time the up-regulation of miR-369-3p in cisplatin (DDP)-resistant nonsmall cell lung cancer (NSCLC) tissues and cells. Its deregulation was found to be correlated to the magnitude of malignancy in well-characterized LCa cells. Functionally, inhibition of miR-369-3p sensitized LCa cells to DDP and suppressed the invasive capability in the presence of DDP treatment, whereas miR-369-3p overexpression promoted DDP resistance and thereby enhanced LCa cells invasiveness. Mechanistically, bioinformatics coupled with luciferase and gain-of-function, loss-of-function assays revealed that miR-369-3p may regulate DDP chemoresistance by directly targeting the 3' untranslated region (UTR) of human solute carrier 35F5 (SLC35F5), as application of miR-369-3p inhibitors or reintroduction of epigenetically silenced SLC35F5 both individually sensitized LCa cells to DDP, but combined treatment with miR-369-3p inhibitors and SLC35F5 overexpression failed to sensitized LCa cells further to DDP-elicited cell death. Our results provide evidence that the oncomiR effect of miR-369-3p may be mediated through disrupting the nucleotide sugar transportation and that SLC35F5 is a key effector of this chemoresistance-promoting activity.

Suppression of EIF4G2 by miR-379 potentiates the cisplatin chemosensitivity in nonsmall cell lung cancer cells.

Although microRNAs and EIF4G2 are both known to play pivotal roles in cancer progression, it remains unknown whether these pathways regulate chemosensitivity in a coordinated manner. Here, we show that miR-379 expression is significantly downregulated in chemoresistant nonsmall cell lung cancer (NSCLC) tissues and cells. Manipulation of miR-379 levels could alter the in vitro and in vivo cisplatin (CDDP) resistance in lung cancer (LCa) cells. Mechanistically, miR-379 potentiated LCa chemosensitivity via modulation of CDDP-induced apoptosis by directly targeting the EIF4G2 3'UTR. Additionally, we observed an inverse correlation between miR-379 and EIF4G2 expression in LCa tissues from patients with CDDP-based chemotherapy. Together, our findings shed new light on the potential involvement of miR-379/EIF4G2 cascade in the pathogenesis of CDDP resistance in LCa.