K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer

AU-rich element-binding proteins (ARE-BPs) offer post-transcriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3′-UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients. Furthermore, cigarette smoke, a leading risk factor for lung cancer, was also identified to be an important contributor to increased KSRP expression. Remarkably, silencing of KSRP decreased cell proliferation, reversed anchorage-independent growth, and reduced migration/invasion, suggesting an oncogenic role for KSRP in lung cancer. Finally, we provide mechanistic evidence that KSRP promotes the down-regulation of Spry4 by a previously unidentified mechanism, i.e. post-transcriptional mRNA regulation.

Download Full-text

Cisplatin-induced hydroxyl radicals mediate pro-survival autophagy in human lung cancer H460 cells

Biological Research ◽

10.1186/s40659-021-00346-2 ◽

2021 ◽

Vol 54 (1) ◽

Author(s):

Somruethai Sumkhemthong ◽

Eakachai Prompetchara ◽

Pithi Chanvorachote ◽

Chatchai Chaotham

Keyword(s):

Lung Cancer ◽

Hydroxyl Radicals ◽

Human Lung ◽

Human Lung Cancer ◽

Radical Scavenger ◽

Apoptosis Resistance ◽

Lung Cancer Patients ◽

Human Lung Cancer Cells ◽

H460 Cells

Abstract Background Accumulated evidence demonstrates cisplatin, a recommended chemotherapy, modulating pro-survival autophagic response that contributes to treatment failure in lung cancer patients. However, distinct mechanisms involved in cisplatin-induced autophagy in human lung cancer cells are still unclear. Results Herein, role of autophagy in cisplatin resistance was indicated by a decreased cell viability and increased apoptosis in lung cancer H460 cells pre-incubated with wortmannin, an autophagy inhibitor, prior to treatment with 50 µM cisplatin for 24 h. The elevated level of hydroxyl radicals detected via flow-cytometry corresponded to autophagic response, as evidenced by the formation of autophagosomes and autolysosomes in cisplatin-treated cells. Interestingly, apoptosis resistance, autophagosome formation, and the alteration of the autophagic markers, LC3-II/LC3-I and p62, as well as autophagy-regulating proteins Atg7 and Atg3, induced by cisplatin was abrogated by pretreatment of H460 cells with deferoxamine, a specific hydroxyl radical scavenger. The modulations in autophagic response were also indicated in the cells treated with hydroxyl radicals generated via Fenton reaction, and likewise inhibited by pretreatment with deferoxamine. Conclusions In summary, the possible role of hydroxyl radicals as a key mediator in the autophagic response to cisplatin treatment, which was firstly revealed in this study would benefit for the further development of novel therapies for lung cancer.

Download Full-text

Role of microRNAs in Lung Carcinogenesis Induced by Asbestos

Journal of Personalized Medicine ◽

10.3390/jpm11020097 ◽

2021 ◽

Vol 11 (2) ◽

pp. 97

Author(s):

Rakhmetkazhy Bersimbaev ◽

Olga Bulgakova ◽

Akmaral Aripova ◽

Assiya Kussainova ◽

Oralbek Ilderbayev

Keyword(s):

Lung Cancer ◽

Expression Profile ◽

Regulation Of Gene Expression ◽

International Agency ◽

Oxygen Species ◽

Lung Carcinogenesis ◽

Mrna Targets ◽

The World ◽

Post Transcriptional Regulation

MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.

Download Full-text

The D-dimer level predicts the prognosis in patients with lung cancer: a systematic review and meta-analysis

Journal of Cardiothoracic Surgery ◽

10.1186/s13019-021-01618-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Mingsheng Ma ◽

Run Cao ◽

Wei Wang ◽

Biying Wang ◽

Yichen Yang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Meta Analysis ◽

High Plasma ◽

Detection Methods ◽

Disease Stage ◽

Lung Cancer Patients ◽

Kaplan Meier ◽

D Dimer

Abstract Objective Although the significance of increased plasma D-dimer levels in activating coagulation and fibrinolysis has been reported, it is still controversial whether it can be used to predict the prognosis of lung cancer patients. This meta-analysis was performed to explore the beneficial role of plasma D-dimer as a prognostic factor in lung cancer patients according to a larger sample capacity. Materials and methods MEDLINE, EMBASE, and Cochrane Central databases were searched from inception to January 2021. The data are mainly hazard ratio(HR) with 95% confidence interval (CI) and Kaplan–Meier survival curves. The publication bias was examined by Egger’s test. Results Finally, a total of 28 studies, enrolling 8452 patients were included in the current meta-analysis. Our results showed that the OS (HR = 1.742, 95%CI:1.542–1.969, P < 0.001) and PFS (HR = 1.385, 95%CI:1.169–1.641, P = 0.003) in the high D-dimer group were significantly lower than those in the low D-dimer group. Subgroup analysis suggested that localization, detection methods and disease stage had an important effect on the prognosis. Conclusion This meta-analysis revealed that the high plasma D-dimer level leads to lower survival than in the low D-dimer level, which might provide an important clue for high plasma D-dimer level as an independent factor of poor prognosis in patients with lung cancer.

Download Full-text

c-Myc shuttled by tumour-derived extracellular vesicles promotes lung bronchial cell proliferation through miR-19b and miR-92a

Cell Death and Disease ◽

10.1038/s41419-019-2003-5 ◽

2019 ◽

Vol 10 (10) ◽

Cited By ~ 9

Author(s):

Cristina Borzi ◽

Linda Calzolari ◽

Anna M. Ferretti ◽

Laura Caleca ◽

Ugo Pastorino ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Patients ◽

Cell Lines ◽

Extracellular Vesicles ◽

Target Genes ◽

In Silico Analysis ◽

Human Lung Cancer ◽

Lung Cancer Patients

Abstract Lung cancer causes approximately one fifth of all cancer deaths. Tumour cells actively communicate with the surrounding microenvironment to support malignant progression. Extracellular vesicles (EVs) play a pivotal role in intercellular communication and modulate recipient cells by delivering their contents, including proteins and nucleic acids such as microRNAs (miRNAs). We isolated EVs from the conditioned medium (CM) of human lung cancer cell lines and plasma of lung cancer patients and cancer-free smokers using an ultracentrifugation method. A significant increase in bronchial HBEC-KRASV12high cell proliferation, confirmed by cell cycle analysis, was observed after treatment with cancer-derived EVs. Lung cancer-derived EVs induced transcription of the pri-miR-92a gene, resulting in the overexpression of mature miR-19b and miR-92a in recipient bronchial cells. Modulation of these two miRNAs using miRNA mimics or inhibitors confirmed their ability to promote proliferation. In silico analysis and experimental validation showed that miR-19b and miR-92a impaired the TGF-beta (TGFB) pathway and identified TGFBRI and TGFBRII as target genes involved in EV-mediated bronchial cell proliferation. Interestingly, the oncoprotein c-Myc, a well-known miR-17-92 cluster activator, was detected only in the EVs derived from lung cancer patients and cell lines and was able to modulate the proliferation of HBEC-KRASV12high recipient cells. These data support the role of c-Myc shuttling in lung cancer-derived EVs in inducing the upregulation of onco-miR-19b and miR-92a expression with concomitant impairment of the TGFB signalling pathway in recipient cells.

Download Full-text

TAO Kinase 3 Overexpression Is a Poor Prognosis Marker for Lung Adenocarcinoma and Predicts Paclitaxel Resistance

10.1101/622621 ◽

2019 ◽

Author(s):

Tsung-Ching Lai ◽

Yi-Chieh Yang ◽

Yu-Chan Chang ◽

Jean Chiou ◽

Ming-Shyan Huang ◽

...

Keyword(s):

Lung Cancer ◽

Progression Free Survival ◽

Disease Recurrence ◽

Paclitaxel Resistance ◽

Poor Overall Survival ◽

Free Survival ◽

Lung Cancer Patients ◽

Prognosis Marker ◽

Highly Correlated

AbstractHigh expression of TAOK3 has been observed in several cancers, but very little about TAOK3-involved mechanisms has been reported. In this study, we investigated the role of TAOK3 in the therapeutic effect of paclitaxel treatment. Protein expression of TAOK3 was evaluated among 121 patients by using immunohistochemical staining. TAOK3 expression was estimated by analyzing the gene’s expression and its correlation with the IC50 of paclitaxel in cells. The expression of TAOK3 in lung cancer was highly correlated with poor overall survival, progression-free survival, and recurrence rate in lung cancer patients. The expression level of TAOK3 was positively correlated with paclitaxel resistance in the lung cancer cell lines. The depletion of TAOK3 could enhance the sensitivity of paclitaxel in lung cancer and vice versa. TAOK3 expression is associated with paclitaxel-resistance and could be a clinical predictor for disease recurrence and a potential therapeutic target in lung cancer.

Download Full-text

Role of LDH, 17-ß-hydroxysteroid dehydrogenase and Myloperoxidase Enzymes in early diagnosis for Lung Cancer patients

International Journal of Pharmaceutical Research ◽

10.31838/ijpr/2020.sp1.272 ◽

2020 ◽

Vol 12 (sp1) ◽

Keyword(s):

Lung Cancer ◽

Early Diagnosis ◽

Cancer Patients ◽

Hydroxysteroid Dehydrogenase ◽

Lung Cancer Patients

Download Full-text

The Role of microRNAs in the Viral Infections

Current Pharmaceutical Design ◽

10.2174/1381612825666190110161034 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4659-4667 ◽

Cited By ~ 4

Author(s):

Mona Fani ◽

Milad Zandi ◽

Majid Rezayi ◽

Nastaran Khodadad ◽

Hadis Langari ◽

...

Keyword(s):

Viral Infections ◽

Rna Viruses ◽

Regulation Of Gene Expression ◽

Molecular Structures ◽

Main Function ◽

Cellular Functions ◽

Viral Genes ◽

Non Coding Rnas ◽

Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

Download Full-text