Humans ; Lung Neoplasms ; genetics ; MicroRNAs ; genetics

Lung cancer is one of the most important malignant tumors of human health and life in the world, and is the leading cause of death in the world. At present, it is believed that it is caused by many factors. Circular RNA (circRNA), as a class of non-coding RNA family, has covalently closed loop structure. CircRNA is abundant in different cells. CircRNAs due to the special structure, with a high degree of specificity, conservation and stability, may have a potential clinical value in the development of lung cancer. The biological function of circRNA is multi-faceted, including miRNA sponge, transcriptional and alternative splicing, protein coding , and so on. Currently, the role and mechanism of circRNA in lung cancer is not very clear. In this paper, the characteristics, function, mechanism and the role of circRNAs in the occurrence and development of lung cancer are reviewed.
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Humans ; Lung Neoplasms ; genetics ; RNA ; genetics

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Humans ; Lung Neoplasms/genetics* ; SMARCB1 Protein

The transformation of non-small cell lung cancer to small cell lung cancer (SCLC) is one of the major resistant mechanisms, especially patients with epidermal growth factor receptor mutant lung adenocarcinoma. Translational SCLC has been found to have similar clinical features to primary SCLC. Chemotherapy was short-term effective for transformational SCLC, with a median survival of only about 1 year. The deletion of RB1 and the change of somatic copy number were associated with SCLC transformation. Although the molecular mechanism of SCLC transformation is still not fully understood. At the same time, the treatment of transformational SCLC also faces great challenges. Currently, chemotherapy regimens for SCLC are the main treatment options for transforming SCLC. Combination therapy, local treatment and strategies for prevention of SCLC transformatio are also being explored. This article will review research advances on the clinical features, molecular mechanism and treatment options of translational SCLC.
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Adenocarcinoma of Lung ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Small Cell Lung Carcinoma/genetics*

Long noncoding RNAs are a group of noncoding RNAs with a length more than 200 nucleotides. Recent studies have revealed that long noncoding RNAs play an important role in the development and progression of cancer. Lung cancer is the leading cause of cancer-related death all over the world. In this article, we review the roles of long noncoding RNAs in lung cancer to provide new insights into the diagnosis and treatment of the disease.
Humans ; Lung Neoplasms ; genetics ; RNA, Long Noncoding ; genetics

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in China. In recent years, therapies for oncogenedrivers and immune checkpoints have proved inspiring. Circular RNA (circRNA), which is a kind of RNA with covalent ring structure relating to stages and metastasis of cancer, has many special biological functions in physiological processes, diseases and so on. Thus, circRNA is expected to be a potential biomarker for cancer prediction and treatment in view of its high conservation and tissue-specific. However, function analysis and regulatory mechanism of circRNA in lung cancer come so far remains unclear and limited literatures are available. In this review, we highlight the research history, formation mechanism, biological function of circRNA and research progress in cancer, especially in lung cancer. We mean to provide theoretical evidences and new ideas for researches on circRNAs in lung cancer.
Animals ; Humans ; Lung Neoplasms ; genetics ; metabolism ; RNA ; biosynthesis ; genetics

Carcinoma, Non-Small-Cell Lung ; genetics ; Exons ; genetics ; Genes, erbB-1 ; genetics ; Humans ; Lung Neoplasms ; pathology

Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; genetics ; metabolism

OBJECTIVES: To evaluate the sensitivity and specificity of immunohistochemistry (IHC) for detecting common epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) and to estimate the cost-effectiveness of IHC testing. METHODS: A total of 208 NSCLC patients were included in the trial, and the EGFR mutation status in the patients were detected by PCR and IHC. Two mutation-specific antibodies against the most common exon 19 deletion (clone SP111) and exon 21 L858R mutation (clone SP125) were tested by using automated immunostainer. A cost-effectiveness analysis model was built for the analysis of optimal detection scheme. RESULTS: With a cutoff value of IHC 1+, the overall sensitivity and specificity of the IHC-based method compared with the PCR-based method were 81.7% (95% CI 72.4% to 89.0%) and 94.7% (95% CI 92.6% to 99.5%), respectively. EGFR 19del mutation was detected by SP111 antibody with a sensitivity of 65.9% (95% CI 49.4% to 79.9%) and specificity of 98.8% (95% CI 95.7% to 99.9%). EGFR L858R mutation was detected by SP125 antibody with a sensitivity of 94.2% (95% CI 84.1% to 98.8%) and specificity of 99.4% (95% CI 96.5% to 100%). The IHC and PCR cost ratio needed to be 1-to-3 or more in our patients to economically justify before the use of IHC. CONCLUSIONS The study confirms an excellent specificity with fairly good sensitivity of IHC and mutation-specific antibodies for common EGFR mutations. It is cost-effective to use IHC method to detect EGFR mutation first when the IHC and PCR cost ratio is 1-to-3 or more in Chinese populations.
Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Humans ; Immunohistochemistry ; Lung Neoplasms/genetics* ; Mutation