Expression of STK11 gene and its promoter activity in MCF control and cancer cells

Alkaf, Asma; Al‐Jafari, Abdulaziz A.; Wani, Tanveer A.; Alqattan, S.; Zargar, Seema

doi:10.1007/s13205-017-1000-6

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…The extrinsic pathway was induced through stk-11 gene expression. It is demonstrated that stk-11 physically associates with p53 and regulates a specific p53-dependent extrinsic apoptosis pathway [40]. Stk-11 protein is present in the cytoplasm as well as the nucleus and migrates to mitochondria during apoptosis [41].…”

Section: Discussionmentioning

confidence: 99%

In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes

Alamery,

AlAjmi,

Wani

et al. 2023

Medicina

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Background and objectives: Non-small cell lung cancer (NSCLC) is often caused by EGFR mutations, leading to overactive cell growth pathways. Drug resistance is a significant challenge in lung cancer treatment, affecting therapy effectiveness and patient survival. However, combining drugs in research shows promise in addressing or delaying resistance, offering a more effective approach to cancer treatment. In this study, we investigated the potential alterations in the apoptotic pathway in A549 cells induced by a combined targeted therapy using tyrosine kinase inhibitors (TKIs) olmutinib and poziotinib, focusing on cell proliferation, differential gene expression, and in silico analysis of apoptotic markers. Methods: A combined targeted therapy involving olmutinib and poziotinib was investigated for its impact on the apoptotic pathway in A549 cells. Cell proliferation, quantitative differential gene expression, and in silico analysis of apoptotic markers were examined. A549 cells were treated with varying concentrations (1, 2.5, and 5 μM) of poziotinib, olmutinib, and their combination. Results: Treatment with poziotinib, olmutinib, and their combination significantly reduced cell proliferation, with the most pronounced effect at 2.5 μM (p < 0.005). A synergistic antiproliferative effect was observed with the combination of poziotinib and olmutinib (p < 0.0005). Quantitative differential gene expression showed synergistic action of the drug combination, impacting key apoptotic genes including STK-11, Bcl-2, Bax, and the Bax/Bcl-2 ratio. In silico analysis revealed direct interactions between EGFR and ERBB2 genes, accounting for 77.64% of their interactions, and 8% co-expression with downstream apoptotic genes. Molecular docking indicated strong binding of poziotinib and olmutinib to extrinsic and intrinsic apoptotic pathway markers, with binding energies of −9.4 kcal/mol and −8.5 kcal/mol, respectively, on interacting with STK-11. Conclusions: Combining poziotinib and olmutinib therapies may significantly improve drug tolerance and conquer drug resistance more effectively than using them individually in lung cancer patients, as suggested by this study’s mechanisms.

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Section: Discussionmentioning

confidence: 99%

In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes

Alamery,

AlAjmi,

Wani

et al. 2023

Medicina

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“…The LKB1 promoter reporter construct was generated by amplifying a 3995-bp fragment of the LKB1 promoter using primers LKB1 prom-XhoI-F 5 -CGGGAATCT CGAGTTGGAAATTCAGTG TGTAGGGCA-3 and LKB1 prom-HindIII-R 5-AAAGCGCAAG CTTCAACAAAAACCCCA AAAGGA-3 resulting in amplification of a product containing XhoI and HindIII restriction enzyme cleavage sites to clone into pGL3-basic firefly luciferase expression vector (Promega, U.S.A.), forming STK11-pGL3 after enzymatic digestion [22].…”

Section: Dual Luciferase Reporter Assaymentioning

confidence: 99%

Retinoid X receptor agonists attenuates cardiomyopathy in streptozotocin-induced type 1 diabetes through LKB1-dependent anti-fibrosis effects

Chai

Lin

Zheng³

et al. 2020

Clinical Science

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Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Retinoid X receptor (RXR) plays an important role in cardiac development and has been implicated in cardiovascular diseases. In the present study, we investigated the effects of RXR agonist treatment on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) and the underlying mechanism. Sprague–Dawley (SD) rats induced by STZ injection were treated with either RXR agonist bexarotene (Bex) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with high glucose (HG) with or without the indicated concentration of Bex or the RXR ligand 9-cis-retinoic acid (9-cis-RA). The protein abundance levels were measured along with collagen, body weight (BW), blood biochemical indexes and transforming growth factor-β (TGF-β) levels. The effects of RXRα down-regulation by RXRα small interfering RNA (siRNA) were examined. The results showed that bexarotene treatment resulted in amelioration of left ventricular dysfunction by inhibiting cardiomyocyte apoptosis and myocardial fibrosis. Immunoblot with heart tissue homogenates from diabetic rats revealed that bexarotene activated liver kinase B1 (LKB1) signaling and inhibited p70 ribosomal protein S6 kinase (p70S6K). The increased collagen levels in the heart tissues of DCM rats were reduced by bexarotene treatment. Treatment of CFs with HG resulted in significantly reduced LKB1 activity and increased p70S6K activity. RXRα mediated the antagonism of 9-cis-RA on HG-induced LKB1/p70S6K activation changes in vitro. Our findings suggest that RXR agonist ameliorates STZ-induced DCM by inhibiting myocardial fibrosis via modulation of the LKB1/p70S6K signaling pathway. RXR agonists may serve as novel therapeutic agents for the treatment of DCM.

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Relationship of Breast Cancer with Other Hormone-Sensitive Cancers

Maurya,

Tripathi,

Mohapatra

et al. 2022

Breast Cancer: From Bench to Personalized Medicine

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Expression of STK11 gene and its promoter activity in MCF control and cancer cells

Abstract: Serine/threonine kinase gene (

Cited by 6 publications

References 23 publications

In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes

In Silico and In Vitro Exploration of Poziotinib and Olmutinib Synergy in Lung Cancer: Role of hsa-miR-7-5p in Regulating Apoptotic Pathway Marker Genes

Retinoid X receptor agonists attenuates cardiomyopathy in streptozotocin-induced type 1 diabetes through LKB1-dependent anti-fibrosis effects

Relationship of Breast Cancer with Other Hormone-Sensitive Cancers

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