Recently, long noncoding RNA SNHG12 has been reported to be dysregulated in various types of cancer. This study investigated its biological function and the underlying molecular mechanism in cervical ...squamous cell carcinoma (CSCC). We found that SNHG12 was significantly overexpressed in CSCC tissues. Further evidence showed that human papillomavirus (HPV) type 16 E6 and E7 might regulate the expression level of SNHG12 by modulating transcription factor c‐Myc. Functional experiments suggested that SNHG12 knockdown dramatically repressed CSCC cells proliferation, migration, and invasion while induced apoptosis in vitro as well as suppressed tumor growth in vivo. In addition, SNHG12 could facilitate epithelial–mesenchymal transition through ERK/Slug/E‐cadherin pathway at least in part. Our findings highlight SNHG12 functions as an oncogenic long noncoding RNA in malignant phenotype and tumorigenesis of CSCC, which implicate it may be a potential target for CSCC treatment.
SNHG12 expression may be driven by the HPV16 E6 and E7 oncogene, through a mechanism that is dependent on c‐Myc activation. SNHG12 contributes to cervical squamous cell carcinoma (CSCC) cells malignant behavior at least partly through activating ERK/Slug signaling pathway, accordingly influences the downstream proteins, for example, E‐cadherin, hence promoting migration, invasion, and epithelial–mesenchymal transition (EMT) in HPV‐infected cells.
The genomic spectrum of biliary tract carcinoma (BTC) has been characterized and is associated with distinct anatomic and etiologic subtypes, yet limited studies have linked genomic alterations with ...personalized therapies in BTC patients.
This study analyzed 803 patients with BTC:164 with gallbladder cancer, 475 with intrahepatic cholangiocarcinoma (ICC) and 164 with extrahepatic cholangiocarcinoma. We determined genomic alterations, mutational signatures related to etiology and histopathology and prognostic biomarkers. Personalized targeted therapies for patients harboring potentially actionable targets (PATs) were investigated.
The median tumor mutation burden (TMB) was 1.23 Mut/Mb, with 4.1% of patients having hypermutated BTCs. Unlike the results obtained from the Western population, the most frequently altered cancer-related genes in our cohort included
(53%),
(26%),
(18%),
(14%) and
(14%). Germline mutations occurred mostly in DNA damage repair genes. Notably, 35.8% of the ICCs harbored aristolochic acid related signatures and an elevated TMB.
and
mutations and amplified 7q31.2 were demonstrated to negatively affect patient prognosis. Moreover, 19 genes were proposed to be PATs in BTCs, with 25.4% of patients harboring these PATs. Forty-six patients received PAT-matched targeted therapies, achieving a 26.1% objective response rate; the median progression-free survival (PFS) was 5.0 months, with 56.8% of patients obtaining PFS benefits.
Extensive genomic diversity and heterogeneity were observed among BTC patients, with contributions according to potential etiology exposures, anatomical subtypes and clinicopathological characteristics. We also demonstrated that patients with refractory BTCs who have PATs can derive considerable benefit from receiving a matched therapy, initiating further prospective clinical trials guided by molecular profiling among this aggressive cancer.
The plant hydraulic network faces several challenges under drought stress. Hydraulic conductivity is one of the major indicators of the hydraulic network's response to drought stress. Here, we review ...our current understanding of the factors directly affecting hydraulic conductivity and the methods used to measure it.
ABSTRACT
N6‐methyladenosine (m6A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m6A writer, reader, and eraser proteins. As ...an m6A writer, the methyltransferase‐like 3‐methyltransferase–like 14 (METTL14)–Wilms tumor 1–associated protein complex dynamically regulates m6A modification and plays important roles in diverse biologic processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation, and their effects on different biologic pathways are still limited. By using both in vivo and in vitro models, we here report that METTL14 is indispensable for postimplantation embryonic development by facilitating the conversion from naive to primed state of the epiblast. Depletion of Mettl14 leads to conspicuous embryonic growth retardation from embryonic d 6.5, mainly as a result of resistance to differentiation, which further leads to embryonic lethality early in gestation. Our data highlight the critical function of METTL14 as an m6A modification regulator in orchestrating early mouse embryogenesis.—Meng, T.‐G., Lu, X., Guo, L., Hou, G.‐M., Ma, X.‐S., Li, Q.‐N., Huang, L., Fan, L.‐H., Zhao, Z.‐H, Ou, X.‐H., OuYang, Y.‐C., Schatten, H., Li, L., Wang, Z.‐B., Sun, Q.‐Y. Mettl14 is required for mouse postimplantation development by facilitating epiblast maturation. FASEB J. 33, 1179–1187 (2019). www.fasebj.org
Programmed death 1 (PD-1) and CD4
CD25
FoxP3
expression in peripheral blood T-cells has been previously reported in various types of cancer. However, the specific variation tendency during surgery ...and chemotherapy, as well as their relationship in gastric cancer patients, still remain unclear. Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape, and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies.
To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3
regulatory T cells (FoxP3
Tregs) before and after surgery or chemotherapy in gastric cancer patients.
Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy. This study also included 29 age-matched healthy donors as a control group. PD-1 expression was detected on lymphocytes, including CD4
CD8
CD45RO
, CD4
CD45RO
, and CD8
CD45RO
lymphocytes as well as regulatory T cells.
We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3
Tregs in gastric cancer patients (
< 0.05). Following D2 gastrectomy, peripheral lymphocytes PD-1 expression and the number of FoxP3
Tregs notably decrease (
< 0.05). However, during postoperative chemotherapy, we only observed a decrease in PD-1 expression on lymphocytes in the CD8
CD45RO
and CD8
CD45RO
populations. Additionally, linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4
CD45RO
FoxP3
activated Tregs (aTregs) on the total peripheral lymphocytes (
= 0.5622,
< 0.0001).
The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.
PD-1/L1 inhibitor-based immunotherapy is currently under investigation in biliary tract cancer (BTC). Apatinib combined with camrelizumab has achieved promising results in various tumor types. The ...aim of this study was to assess the safety and efficacy of apatinib plus camrelizumab for advanced biliary tract cancer patients who have received previously treatments.
This prospective, non-randomized, open-label trial was conducted at Peking Union Medical College Hospital (PUMCH). All included patients received apatinib orally at 250 mg per a day and camrelizumab intravenously at 200 mg every three weeks until disease progression or intolerable toxicity occurred. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0).
A total of 22 patients were consecutively enrolled from 1st December, 2018 until 1st August, 2020. Among 21 patients for whom we could conduct efficacy evaluations, no patients achieved a complete response (CR), 4 patients (19%) achieved partial response (PR), and 11 patients had stable disease with a disease control rate of 71.4%. The median overall survival was 13.1 months (95% CI, 8.1-18.2), and the median progression-free survival was 4.4 months (95% CI, 2.4-6.3). All patients experienced treatment related AEs, and grade 3 or 4 AEs occurred in 14 (63.6%) of 22 patients. No treatment related deaths were observed.
This is the first report focusing on the efficacy and safety of camrelizumab plus apatinib in pretreated biliary tract cancer patients. The finding suggests this regimen has favorable therapeutic effects with relatively manageable toxicity. Further trials with a control arm are required to investigate.
identifier NCT04642664.
Key message
Regional association analysis of 50 re-sequenced Chinese semi-winter rapeseed accessions in combination with co-expression analysis reveal candidate genes affecting oil accumulation in
...Brassica napus
.
One of the breeding goals in rapeseed production is to enhance the seed oil content to cater to the increased demand for vegetable oils due to a growing global population. To investigate the genetic basis of variation in seed oil content, we used 60 K
Brassica
Infinium SNP array along with phenotype data of 203 Chinese semi-winter rapeseed accessions to perform a genome-wide analysis of haplotype blocks associated with the oil content. Nine haplotype regions harbouring lipid synthesis/transport-, carbohydrate metabolism- and photosynthesis-related genes were identified as significantly associated with the oil content and were mapped to chromosomes A02, A04, A05, A07, C03, C04, C05, C08 and C09, respectively. Regional association analysis of 50 re-sequenced Chinese semi-winter rapeseed accessions combined with transcriptome datasets from 13 accessions was further performed on these nine haplotype regions. This revealed natural variation in the
BnTGD3
-A02 and
BnSSE1
-A05 gene regions correlated with the phenotypic variation of the oil content within the A02 and A04 chromosome haplotype regions, respectively. Moreover, co-expression network analysis revealed that
BnTGD3
-A02 and
BnSSE1
-A05 were directly linked with fatty acid beta-oxidation-related gene
BnKAT2
-C04, thus forming a molecular network involved in the potential regulation of seed oil accumulation. The results of this study could be used to combine favourable haplotype alleles for further improvement of the seed oil content in rapeseed.
Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important ...medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.
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