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Long non-coding RNA (lncRNA) is extremely complex in the occurrence and metastasis of various types of cancer.
, the detailed molecular mechanism of lncRNA in non-small cell lung cancer (NSCLC) is not uncertain.
September 2, 2020, Associate Professor Sun Chengchao, Professor Li Degas and Professor He Qiqiang of Wuhan University's School of Health jointly published an online publication entitled "FOXC1-mediated LINC00301 helpers tumor progression and triggers an immune-suppressing microenvironment in non-non-Small cell lung cancer by regulating the HIF1 alpha pathway" research paper, which reveals the carcinogenic effects of LINC00301 in NSCLC clinical specimens, cells and animal levels, and details the specific role and molecular regulatory mechanisms of LINC00301 in NSCLC tumor occurrence, development, metastasis and immunosuppression microencular formation. It provides a new understanding for tumor occurrence and immunotherapy of NSCLC.
combined with LNA technology, LINC00301 has the potential to be a target for NSCLC diagnostic therapy.
non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the world, it is urgent to clarify the mechanism of NSCLC occurrence and development and improve the diagnosis and treatment of NSCLC.
long-chain non-coding RNA (lncRNA) is a class of RNA that is larger than 200 nucleotide units (nt) in length and does not have complete protein coding capabilities and has long been considered a genetic "noise".
with the rise of the Human Genome Project and second-generation sequencing, the role of lncRNA in human diseases, especially cancer, is being revealed.
recent studies have found that they are widely involved in the pathophysiological processes of multiple cancers and are expected to act as clinical prognosis or diagnostic markers.
with the development of locked nucleic acid (LNA) technology, lncRNA also has the potential to be a target for clinical treatment.
study, the team first discovered and reported a new lncRNA, LINC00301, which is significantly higher in specific expression in NSCLC tumor samples and cell line and is closely related to the prognostication of NSCLC patients.
in vitro and in vitro studies show that LINC00301 promotes cell proliferation, migration and invasion in NSCLC, and inhibits cell cycle blocking and apoptosis.
the study found that the transcription factor FOXC1 specifically mediated the expression of LINC00301 in NSCLC.
Through the RNA in-place hybridization experiment (FISH) found that LINC00301 is present in both the cytocytes and nucleus of NSCLC, but the ratio of LINC00301 in the nucleus is higher than the ratio in the cytotyte, so it is speculated that LINC00301 will play a regulatory role in both the plasma and the nucleus.
bioinsynomic prediction and RNA molecular biology experiments, it was found that linC00301's 83-123 nucleotide bits could be directly related to the flavoring enhancer 2 (EZH2) of 612-2 727 Amino acid site-specific binding, LINC00301 will form a complex with EZH2 and raise the latter rich in ELL protein-related factor 2 (EAF2) promoting the EAF2 gene promoter no. 1395-?? H3K27me3 occurs at 1388 nucleotide site, which inhibits transcriptional expression of EAF2.
considering that EAF2 binds directly to the stable von Hippel-Lindau (pVHL) protein, in NSCLC cells, the reduced EAF2 increases the expression of HIF1 alpha by regulating pVHL.
addition, LINC00301 can also be used as a competitive endogenetic RNA (ceRNA) of miR-1276 in the cytostyle to relieve the translation inhibition of miR-1276 to HIF1 alpha, and ultimately to increase the expression of HIF1 alpha in NSCLC cells.
At the same time, LINC00301 promotes the secretion of TGF-beta by raising the HIF1 alpha signaling pathway, which raises and increases the accumulation of regulatory T cells (regulatory T cells, Treg) in the tumor micro-environment, reducing the number of effect CD8 plus Granzyme B-T cells in tumors, and forming an immunosuppressive micro-environment in NSCLC.
, this study reveals the carcinogenic effect of LINC00301 in NSCLC clinical specimens, cells and animal levels, and elaborates the specific role and molecular regulatory mechanism of LINC00301 in NSCLC tumor occurrence, development, metastasis and immunosuppression microencular formation, which provides a new understanding for NSCLC tumor occurrence and immunotherapy.
combined with LNA technology, LINC00301 has the potential to be a target for NSCLC diagnostic therapy.
long-chain non-coding RNA LINC00301 in non-small cell lung cancer (NSCLC) role model map article by the National Natural Science Foundation (81802285), postdoctoral innovation talent support program (BX201700178), China Postdoctoral Science Fund (2017M620340), Hubei Provincial Health Planning Commission Medical Research Fund (WJ2019Q039) ), supported by the Central University Special Basic Research Fund (201530502020202, 2042018kf0025), Wuhan Municipal Health planning commission Medical Research Fund (WG18Q01), Wuhan University Talent Launch Fund, Wuhan University Health College Independent Research Fund (ZZKY0014) and the Open Laboratory Open Fund for Occupational Hazard Identification and Control in Hubei Province (OHIC2017Y02).
, Associate Professor sun Chengchao of the
Institute of Health, 2017 doctoral student Zhu Wei and Dr. Li Shuxuan of Wuhan Institute of Occupational Disease Prevention and Control are co-authors, and Associate Professor Sun Chengchao, Professor Li Dega and Professor He Qiqiang are co-authors of the newsletter.
study was also conducted by the University of Texas M.D. Important guidance from Professors Liuqing Yang and Chunru Lin of anderson Oncology Centre.
.