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1.
Clin Transl Oncol ; 24(12): 2272-2284, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36008615

ABSTRACT

Lung cancer is one of the most common malignant tumors with growing morbidity and mortality worldwide. Several treatments are used to manage lung cancer, including surgery, radiotherapy and chemotherapy, as well as molecular-targeted therapy. However, the current measures are still far from satisfactory. Therefore, the current research should focus on exploring the molecular mechanism and then finding an effective treatment. Interestingly, we and others have embarked on a line of investigations focused on the mechanism of lung cancer. Specifically, lncRNA small nucleolar RNA host gene has been shown to be associated with biological characteristics and therapeutic resistance of lung cancer. In addition, small nucleolar RNA host genes may be used as diagnostic biomarker in the future. Herein, we will provide a brief review demonstrating the importance of small nucleolar RNA host genes in lung cancer, especially non-small cell lung cancer. Although lncRNA has shown a crucial role in tumor-related research, a large number of studies are needed to validate its clinical application in the future.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , RNA, Long Noncoding , Biomarkers , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Small Nucleolar
2.
J Exp Med ; 218(9)2021 09 06.
Article in English | MEDLINE | ID: mdl-34254999

ABSTRACT

Astrocytes, a major glial cell type in the brain, play a critical role in supporting the progression of medulloblastoma (MB), the most common malignant pediatric brain tumor. Through lineage tracing analyses and single-cell RNA sequencing, we demonstrate that astrocytes are predominantly derived from the transdifferentiation of tumor cells in relapsed MB (but not in primary MB), although MB cells are generally believed to be neuronal-lineage committed. Such transdifferentiation of MB cells relies on Sox9, a transcription factor critical for gliogenesis. Our studies further reveal that bone morphogenetic proteins (BMPs) stimulate the transdifferentiation of MB cells by inducing the phosphorylation of Sox9. Pharmacological inhibition of BMP signaling represses MB cell transdifferentiation into astrocytes and suppresses tumor relapse. Our studies establish the distinct cellular sources of astrocytes in primary and relapsed MB and provide an avenue to prevent and treat MB relapse by targeting tumor cell transdifferentiation.


Subject(s)
Astrocytes/pathology , Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Animals , Bone Morphogenetic Proteins/metabolism , Bone Morphogenetic Proteins/pharmacology , Cell Transdifferentiation/drug effects , Cerebellar Neoplasms/genetics , Cerebellar Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Hedgehog Proteins/metabolism , Humans , Medulloblastoma/genetics , Medulloblastoma/metabolism , Mice, Transgenic , Patched-1 Receptor/genetics , Patched-1 Receptor/metabolism , Phosphorylation , Pyrazoles/pharmacology , Pyrimidines/pharmacology , SOX9 Transcription Factor/metabolism , Single-Cell Analysis , Xenograft Model Antitumor Assays
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