scholarly journals The Association of microRNA-34a With High Incidence and Metastasis of Lung Cancer in Gejiu and Xuanwei Yunnan

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Chen ◽  
Chun Hou ◽  
Liu-xin Zhao ◽  
Qiu-chen Cai ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Yunnan Province ◽  
Molecular Mechanisms ◽  
Small Cell Lung Carcinoma ◽  
Regulatory Gene ◽  
Squamous Carcinoma ◽  
Migration And Invasion ◽  
Cell Lung Carcinoma ◽  
Tumorigenesis And Progression

The incidence and associated mortality of lung cancer in tin miners in Gejiu County and farmers in Xuanwei Country, Yunnan Province have been very high in the world. Current published literatures on the molecular mechanisms of lung cancer initiation and progression in Gejiu and Xuanwei County are still controversial. Studies confirmed that microRNA-34a (miR-34a) functioned as a vital tumor suppressor in tumorigenesis and progression. However, the role and precise mechanisms of miR-34a and its regulatory gene network in initiation and progression of lung cancer in Gejiu and Xuanwei County, Yunnan Province, have not been elucidated. In the current study, we first found that miR-34a was downregulated in Gejiu lung squamous carcinoma YTMLC-90, Xuanwei lung adenocarcinoma XWLC-05, and other non-small cell lung carcinoma (NSCLC) cell lines, and miR-34a overexpression inhibited cell proliferation, migration and invasion, as well as induced cell apoptosis in YTMLC-90 and XWLC-05 cells. Our findings revealed that miR-34a is critical and cannot be considered as the area-specific non-coding RNA in initiation and progression of lung cancer in Gejiu and Xuanwei County. Next we revealed that miR-34a overexpression suppressed lung cancer growth and metastasis partially via increasing PTEN but reducing CDK6 expression that might lead to subsequent inactivation of PI3K/AKT pathway. Furthermore, our findings demonstrated that YY1 functioned as a tumor suppressor gene in initiation and progression of lung cancer in Gejiu and Xuanwei County. In conclusion, our findings in the study confirmed that miR-34a overexpression could simultaneously suppress tumor growth and metastasis and play a vital role in tumorigenesis and progression of NSCLC via increasing PTEN and YY1 expression, but decreasing CDK6. Most interestingly, our findings also raised doubts about the current ideas about these area-specific diseases.

scholarly journals Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ling Wang ◽  
Ayrianna Sparks-Wallace ◽  
Jared L. Casteel ◽  
Mary E. A. Howell ◽  
Shunbin Ning
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Lung Carcinoma ◽  
Membrane Trafficking ◽  
Small Cell Lung Carcinoma ◽  
Regulatory Protein ◽  
Small Cell ◽  
Expression Level ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), with a considerable contribution from its promoter methylation rather than its gene mutations. The Limd1 gene undergoes mutation only at a low rate in NSCLC (0.712%). We have further identified LIMD1-associated molecular signatures in NSCLC, including its natural antisense long non-coding RNA LIMD1-AS1 and a pool of membrane trafficking regulators. We have also identified a subgroup of tumor-infiltrating lymphocytes, especially neutrophils, whose tumor infiltration levels significantly correlate with LIMD1 level in both LUAD and LUSC. However, a significant correlation of LIMD1 with a subset of immune regulatory molecules, such as IL6R and TAP1, was only found in LUAD. Regarding the clinical outcomes, LIMD1 expression level only significantly correlates with the survival of LUAD (p<0.01) but not with that of LUSC (p>0.1) patients. These findings indicate that LIMD1 plays a survival role in LUAD patients at least by acting as an immune regulatory protein. To further understand the mechanisms underlying the tumor-suppressing function of LIMD1 in NSCLC, we show that LIMD1 downregulation remarkably correlates with the deregulation of multiple pathways that play decisive roles in the oncogenesis of NSCLC, especially those mediated by EGFR, KRAS, PIK3CA, Keap1, and p63, in both LUAD and LUSC, and those mediated by p53 and CDKN2A only in LUAD. This study has disclosed that LIMD1 can serve as a survival prognostic marker for LUAD patients and provides mechanistic insights into the interaction of LIMD1 with NSCLC, which provide valuable information for clinical applications.

scholarly journals Molecular Profiling in Non–Small Cell Lung Cancer: A Step Toward Personalized Medicine

2013 ◽  
Vol 137 (4) ◽  
pp. 481-491 ◽  
Author(s):  
Kirtee Raparia ◽  
Celina Villa ◽  
Malcolm M. DeCamp ◽  
Jyoti D. Patel ◽  
Minesh P. Mehta
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Small Cell Lung Carcinoma ◽  
Locally Advanced ◽  
Small Cell ◽  
Driver Mutations ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Context.—Lung carcinoma is the result of sequential accumulation of genetic and epigenetic changes. Lung adenocarcinoma is a heterogeneous disease with diverse somatic mutations, and several of them include the so-called driver mutations, which may serve as “druggable” therapeutic targets. Thus, development of personalized approaches for the treatment of non–small cell lung carcinoma (NSCLC) mandates that pathologists make a precise histologic classification inclusive of routine molecular analysis of such tumors. Objective.—To address the molecular mechanisms underlying NSCLC and how this knowledge reflects the multidisciplinary approach in the diagnosis and management of these patients. We will also summarize the current available and investigational personalized therapies for patients with resectable early-stage, unresectable locally advanced, and metastatic NSCLC. Data Sources.—Peer-reviewed published literature and personal experience. Conclusions.—There are multiple mechanisms involved in the pathogenesis of lung cancer, which operate in parallel and involve pathways of activation and inhibition of various cellular events. Further research is essential to characterize the histologic and mutational profiles of lung carcinomas, which will ultimately translate into improved and more personalized therapeutic management of patients with lung cancer.

scholarly journals KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer

2015 ◽  
Vol 37 (1) ◽  
pp. 201-213 ◽  
Author(s):  
Jun Ma ◽  
Ning Wang ◽  
Yurong Zhang ◽  
Cun Wang ◽  
Tianxiang Ge ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Small Cell ◽  
Nuclear Accumulation ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Background/Aims: Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers. Methods: Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research. Results: We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27), inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells. Conclusions: These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

scholarly journals Effect of miR-21 on Apoptosis in Lung Cancer Cell Through Inhibiting the PI3K/ Akt/NF-κB Signaling Pathway in Vitro and in Vivo

2018 ◽  
Vol 46 (3) ◽  
pp. 999-1008 ◽  
Author(s):  
Bing Zhou ◽  
Dimin Wang ◽  
Gaozhong Sun ◽  
Fuyang Mei ◽  
Yong Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Small Cell Lung Carcinoma ◽  
Critical Role ◽  
Migration And Invasion ◽  
Tunel Staining ◽  
Cell Lung Carcinoma ◽  
Induced Apoptosis

Background/Aims: Lung cancer is one of the most common malignancies in the world. Apoptosis-stimulating protein of p53 (ASPP2), a tumorigenesis related protein, plays a critical role in the initiation and development of various types of cancers. However, the effect of ASPP2 on lung cancer remains unknown. The purpose of this study aims to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. Methods: In the study, migration and invasion assays, apoptosis assay, caspase activity assay, TUNEL staining, real time PCR and western blot were used to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. Results: We demonstrated that the miR-21 inhibitor induced apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in non-small cell lung carcinoma (NSCLC). Moreover, ASPP2 was directly targeted by miR-21 in NSCLC cells. Down-regulation of miR-21 suppressed cell migration and invasion, as well as the EMT signaling pathway in NSCLC cells. Furthermore, the miR-21 inhibitor induced cell apoptosis via the caspase dependent pathway in NSCLC cells. The miR-21 inhibitor enhanced caspase-3, 8, 9 activity in NSCLC cells. In addition, the caspase inhibitor significantly reduced the apoptosis induced by the miR-21 inhibitor in NSCLC cells. Conclusions: Our results revealed that the miR-21 inhibitor could induce apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in human NSCLC cells, and might serve as a therapeutic strategy to treat NSCLC.

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors

2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 247-254 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Content Type ◽  
The Brain ◽  
Fine Print

Object. Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. Methods. A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. Conclusions. Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

New lung cancer treatment strategy with molecular target of PKCeta

Impact ◽  
2019 ◽  
Vol 2019 (8) ◽  
pp. 56-58
Author(s):  
Motoi Ohba
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Growth Factor Receptor ◽  
Small Cell ◽  
Surgical Removal ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Nucleotide Mutation

Lung cancer is one of the most prevalent and lethal forms of the disease accounting for almost 20 per cent of all deaths from cancer. It is therefore the leading cause of cancer death in men and second most fatal in women. There are between 1.5 and 2 million new cases of cancer globally every year. A similar number die from the disease annually. There are two forms of lung cancer – small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). SCLC is the more aggressive form being faster growing and more metastatic, however it also responds more effectively to treatments such as chemotherapy. NSCLC is the more common form of the disease, accounting for 85 per cent of cases. They develop more slowly than SCLCs, however they are largely unresponsive to chemotherapy and require precise surgical removal. Both present a huge medical problem in terms of diagnosis and treatment. Due to its far higher prevalence, NSCLC is the most studied of the two forms. A chemotherapeutic treatment has been developed that targets the epidermal growth factor receptor (EGFR). EGFR is majorly upregulated in most cases and plays a key role in the tumour's growth and survival. The treatment blocks the receptor and is usually very effective in the first instances. However, it is typically unable to clear the cancer as a single nucleotide mutation is capable of rendering the inhibitor unable to act on the receptor. Therefore, the cancer returns and continues to develop. New treatments are also required. This is the work of Dr Motoi Ohba of the Advanced Cancer Translational Research Institute, Showa University, Japan. His work is aimed at both uncovering novel targets for cancer treatment and finding and developing molecules that could effectively manipulate these targets.

Evidence for a tumor suppressor gene on chromosome 3 in human non-small cell lung carcinoma

1995 ◽  
Vol 84 (2) ◽  
pp. 154
Author(s):  
Jay D. Hunt ◽  
Joseph R. Testa ◽  
Daniel F. McCallister ◽  
David I. Smith ◽  
Jannette Hutchinson ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Suppressor Gene ◽  
Small Cell ◽  
Chromosome 3 ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Targeted therapeutics for non small cell lung carcinoma

2019 ◽  
Author(s):  
◽  
Soumavo Mukherjee
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Environmental Pollutants ◽  
Ether Linkage ◽  
University Of Missouri ◽  
Cell Lung Carcinoma ◽  
Age Of Diagnosis ◽  
The University ◽  
Gene Expression Levels

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] "Lung carcinoma, also known as lung cancer, is a malignant tumor of lungs characterized by uncontrolled call growth in lung tissue. Tobacco smoking is the reason for nearly 85% of cases of lung cancer. The rest 10-15% are usually a combination of genetic factors, secondhand smoke, environmental pollutants, asbestos and radon gas exposure. Chest radiography and CT scan with confirmation by biopsy are the ways to detect the cancer. The type of cancer, degree of spread and the overall health weigh in on the outcome and eventual possible cure. Still now, most cases are not curable. Surgery, chemotherapy and radiotherapy are the treatments of choice for all types of lung cancer. Being the most common form of cancer in men and second most common form in women, after breast, data of the year 2012 showed 1.8 million incidences of lung cancer resulting to 1.6 million deaths worldwide, with the most common age of diagnosis being 70 years. 5-year survival rate in USA is 17.4%. ... Studies has been done to unravel the downstream effect after knocking down the oncogene via siRNA(42). Malignant cells have a number of secondary pathways, along with the primary pathway, which remain dormant till the disruption of the primary pathway(43). A complex mechanism controls this function which is triggered by the change in downstream protein and gene expression levels. This makes the cancer cells develop drug resistance(44). In this project, we developed a gelatin-based nanoparticle (GelNP) that will act as a vehicle to deliver targeted siRNAs against NSCLC cells in combination with Cisplatin. The cetuximab (Ab), an EGFR targeting antibody, shall be attached to the surface. The AXL and FN14 SiRNAs shall be conjugated to the antibody by the thio-ether linkage. The cetuximab antibody shall be used to specifically target the cell and also to protect the siRNAs from degradation. We predict that 146kDa cetuximab antibody will shield the 15kDa siRNAs and prevent it from exposure to environment. Since AXL and FN14 has been observed to be related to EGFR, we hypothesize that knocking down AXL and FN14 will block EGFR and thus allow the TKI to continue its course of therapeutic action."--Introduction.

scholarly journals GSTP1 Ile105Val polymorphism among North Indian lung cancer patients treated using monotherapy and poly-pharmacy

2021 ◽  
pp. 096032712110594
Author(s):  
Harleen Kaur Walia ◽  
Navneet Singh ◽  
Siddharth Sharma
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Small Cell Lung Carcinoma ◽  
Predictive Biomarker ◽  
Hematological Toxicity ◽  
Cell Lung Carcinoma ◽  
Mutant Genotype ◽  
Lung Cancer Patients ◽  
Platinum Based Chemotherapy ◽  
Increased Risk

Background Genetic polymorphism within the P1 isoenzyme of the Glutathione-S-Transferase (GST) family is found to modulate and alter the enzyme activity of GSTP1 protein and thus may result in a change of sensitivity to platinum-based chemotherapy. We investigated the relationship between GSTP1 Ile 105 Val polymorphisms and overall survival, treatment response, and for both hematological and non-hematological toxicity of advanced North Indian lung cancer patients undergoing platinum-based double chemotherapy. Methods The polymorphism of GSTP1 Ile 105 Val in North Indian lung cancer patients was assessed by polymerase chain reaction-restriction fragment length polymorphism. A total of 682 lung cancer patients were enrolled in the study, and it was observed that patients who were carrying both the mutant alleles ( Val/Val) for the GSTP1 polymorphism showed a higher trend of median survival time (MST) as compared to the patients bearing the wild type of genotype (Ile/Ile) (MST = 8.30 vs. 7.47, p = 0.56). Based on toxicity profiling, we observed that lung cancer patients with the mutant genotype of GSTP1 (Val/Val) had an increased risk of leukopenia (OR = 2.41; 95% CI = 1.39-4.18, p = 0.001) as compared to subjects carrying both copies of the wild alleles (Ile/Ile). Our data suggested that patients with heterozygous genotype (Ile/Val) had a 2.14-fold increased risk of developing severe anemia (OR = 2.14, 95% CI = 0.97-4.62, p = 0.03). Our data also showed that in small cell lung carcinoma (SCLC) patients' polymorphism of GSTP1 was associated with thrombocytopenia (χ2 test = 7.32, p = 0.02). Conclusions Our results suggest that GSTP1 Ile105Val polymorphism could be a predictive biomarker for hematological toxicity, like leukopenia and anemia, but not thrombocytopenia or neutropenia

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