Noblenordentoft0776
To investigate the genetic mutations in both tumor and marginal tissues in patients with non-small cell lung cancer (NSCLC), and to evaluate the potential prognostic value in patients with margins gene positive.
Next-generation sequencing (NGS) technique was used to detect genetic mutation in tumor and marginal tissues of the bronchus in 88 patients with NSCLC. Correlation of genetic mutations with pathology, lymph node metastasis, disease-free survival and overall survival was analyzed.
Of the 88 patients, 83 cases (94.3%) had gene mutations in the tumor samples and 12 cases (13.6%) had genetic alterations in their margins. Most of the gene mutations detected were cancer drivers. Six common driver genes between tumor and marginal tissues were identified, including
,
,
,
,
, and
. Kaplan-Meier analysis revealed that the median disease-free survival (DFS) was significantly shorter in patients with detectable gene mutations in marginal tissues compared with patients without mutations in margins (30.7 versus 24.4 months, log-rank
= 4.78,
=0.029). Consistently, a shorter median OS was observed in patients harboring gene mutations in margins compared with patients with no mutations in margins (49.1 versus 32.2 months, log-rank
= 3.669,
=0.055).
These findings identify the presence of oncogenic alterations in microscopically negative margins in NSCLC patients associated with elevated risk of relapse and shorter survival time. Thus, examination of microscopically negative margins by NGS represents a valuable approach to predict the clinical outcome of NSCLC patients.
These findings identify the presence of oncogenic alterations in microscopically negative margins in NSCLC patients associated with elevated risk of relapse and shorter survival time. Thus, examination of microscopically negative margins by NGS represents a valuable approach to predict the clinical outcome of NSCLC patients.
MicroRNAs have been identified as major regulators and therapeutic targets of glioblastoma (GBM). It is thus meaningful to study the miRNAs differentially expressed (DE-miRNAs) in GBM.
We performed a meta-analysis of previously published microarray data using the R-based "metaMA" package to identify DE-miRNAs.The biological processes of the DE-miRNAs were then analyzed using FunRich. KEGG pathways of the DE-miRNAs gene targets were analyzed by mirPath V.3. Luciferase activity assay was performed to validate that
is a direct target of
. Flow cytometry was used to detect the effects of
on GBM cell proliferation, apoptosis and cell cycle.
DE-miRNAs in blood and brain tissue from GBM were identified. "Type I interferon signaling pathway" and "
and
signaling network" were the most significantly enriched biological processes shared by all GBM types. In KEGG pathway analysis, DE-miRNAs both in blood and tissue show altered fatty acid biosynthesis. Further validation shows
regulates fatty acid metabolism by directly targeting
gene. In addition, our data revealed an accelerated cell cycle and an anti-apoptotic role for OXSM in glioma cells, which has not been reported. Finally, we confirmed that
inhibitor antagonized the effect of downregulation of
on cell cycle and apoptosis of GBM cells.
We revealed that
, down-regulated in GBM, may affect the biogenesis and rapid proliferation of glioma cells by regulating the level of
, providing new insights into understanding the pathogenesis of GBM and developing strategies to improve GBM prognosis.
We revealed that hsa-miR-338-3p, down-regulated in GBM, may affect the biogenesis and rapid proliferation of glioma cells by regulating the level of OXSM, providing new insights into understanding the pathogenesis of GBM and developing strategies to improve GBM prognosis.
Circular RNAs (circRNAs) have been reported to be involved in regulating the development of breast cancer. Paclitaxel (PTX) can be used for the chemotherapy of breast cancer. The study aimed to explore the role and mechanism of circ_0006528 in PTX-resistant breast cancer progression.
The levels of circ_0006528, microRNA-1299 (miR-1299) and cyclin-dependent kinase 8 (
) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). RNase R treatment was used to confirm that the circ_0006528 was a circular RNA. PTX resistance and cell proliferation were determined by Cell counting kit-8 (CCK-8) assay. Cell apoptosis, migration and invasion were analyzed by flow cytometry and Transwell assays, respectively. The levels of all proteins were examined by Western blot. The interaction between circ_0006528 and miR-1299 or
was predicted by online database confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft mice model was constructed to reveal the role of circ_ing miR-1299.
Circ_0006528 partially contributed to PTX resistance of breast cancer cells through up-regulating CDK8 expression by sponging miR-1299.
Rho-GTPases and their activators, guanine nucleotide exchange factors (GEFs), are increasingly being recognized as essential mediators of oncogenic signaling. Although it is known that P-Rex1, a member of the
family of GEFs for the Rac small GTPase, contributes to the migration of cancer cells, its exact role in liver cancer and the underlying mechanisms remain unclear.
Public datasets from the Gene Expression Omnibus database (GEO) and clinical liver cancer samples were analyzed to explore the expression of P-Rex1. P-Rex1 knockdown and overexpression cell lines were established using a recombinant lentiviral transfection system. Ferrostatin-1 in vivo BrdU and colony formation assays were performed to determine cell viability. Migratory capacity was analyzed using a transwell migration assay and an in vitro wound-healing assay. Nude mice bearing subcutaneous xenograft tumors were established to determine the effects of P-Rex1 on tumorigenesis in vivo. The role of P-Rex1 in hepatocarcinogenesis was determined through Westernment.
These results support the role of P-Rex1 as a novel player in liver cancer, which suggest that targeting P-Rex1 may provide a potential strategy for liver cancer treatment.
