Genome Med: Wu Dasun Chengchao and others reveal the important role of LINC00301 in the progress of non-small cell lung cancer and tumor immunity.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death among the world, but the specific mechanisms by which it occurs still need to be further clarified.
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.
September 2, 2020, a team of professors Sun Chengchao, Li Degas and He Qiqiang of Wuhan University's School of Health published a research paper entitled: FOXC1-mediated LINC00301 in the journal MEDICINE.
This study reveals the carcinogenic effect of LINC00301 in NSCLC clinical specimens, cells and animal levels, elaborates the specific role and molecular regulatory mechanism of LINC00301 in NSCLC tumor occurrence, development, metastasis and immunosuppression microencular formation, and 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.
in this study, the team first discovered and reported a new lncRNA, LINC00301, which has significantly higher specific expressions 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.
by bioinsynomic prediction and RNA molecular biology experiments, it was found that linC00301's 83-123 nucleotide bits can be directly combined with the flavoring enhancer 2 (EZH2) 612-727 amino acid bit specificity, LINC00 301 will form a complex with EZH2 and collect the latter rich in ELL protein-related factor 2 (EAF2) promoting H3K27me3 at the 1395-1388 nucleotide site of the EAF2 gene promoter, thereby inhibiting 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 cell, Treg) in the tumor micro-environment, reducing the number of effect CD8-Granzyme B-T cells in tumors and forming an immunosuppressive micro-environment in NSCLC.
the role of LINC00301 in non-small cell lung cancer (NSCLC), the study revealed the carcinogenic effects of LINC00301 in clinical specimens as well as at the cellular and animal levels, and analyzed FOXC1/LINC00301/EZH The potential effects and mechanisms of 2/EAF2/pVHL/HIF-1 alpha and FOXC1/LINC00301/miR-1276/HIF-1 alpha pathfly provide new insights and potential therapeutic targets for non-small cell lung cancer.
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