Shahwar, D. | Iqbal, M.J. | Nisa, M.-U. | Todorovska, M. | Attar, Rukset | Sabitaliyevich, U.Y. | Xu, B.

Review | 2019 | International Journal of Molecular Sciences20 ( 8 )

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression . . . of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers. © 2019 by the authors. Licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Butt, G. | Yaylim, I. | Attar, Rukset | Aras, A. | Romero, M.A. | Qureshi, M.Z. | Farooqi, A.A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1152 , pp.365 - 375

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have “split-personalities”. These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of . . . regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Farooqi, A.A. | Qureshi, M.Z. | Attar, Rukset | Alhewairini, S.S. | Fayyaz, S. | Sabitaliyevich, U.Y. | Alaaeddine, N.

Review | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 6 ) , pp.1 - 5

Central dogma of molecular biology, a term coined by Francis Crick in 1958 was considered to be the cornerstone of molecular biology unless molecular biologists challenged the idea after ground-breaking discovery of non-coding RNAs. Discovery of microRNAs marked a new era and revolutionized our understanding related to puzzling mysteries about intermediate steps between transcription and translation. Technological advancements have spawned a multitude of platforms for profiling of long-noncoding RNAs and miRNAs in different cancers. Detailed investigation of mRNA targets of miRNAs has enabled high-order analyses of interconnected ne . . .tworks and revealed affected pathways in different cancers. miR-143 has emerged as a multi-talented tumor suppressor microRNA having considerable ability to inhibit and prevent cancer via regulation of myriad of oncogenes. In this review, we will summarize most recent evidence related to characteristically unique ability of miR-143 to target different oncogenic mRNAs in different cancers. We will also comprehensively discuss how scientists have identified multiple long non-coding RNAs reportedly involved in promoting the expression of oncogenes by interfering with miR-143 mediated targeting of these oncogenes. Because of excellent ability of miR-143 to effectively target oncogenic mRNAs, researchers have started to focus on use of miR-143 mimics to restore expression of miR-143 in various cancers Daha fazlası Daha az

Farooqi, A.A. | Qureshi, M.Z. | Khalid, S. | Attar, Rukset | Martinelli, C. | Sabitaliyevich, U.Y. | Xu, B.

Article | 2019 | Cancers11 ( 4 ) , pp.1 - 5

There has been a renewed interest in the identification of natural products having premium pharmacological properties and minimum off-target effects. In accordance with this approach, natural product research has experienced an exponential growth in the past two decades and has yielded a stream of preclinical and clinical insights which have deeply improved our knowledge related to the multifaceted nature of cancer and strategies to therapeutically target deregulated signaling pathways in different cancers. In this review, we have set the spotlight on the scientifically proven ability of berberine to effectively target a myriad of d . . .eregulated pathways. © 2019 by the authors. Licensee MDPI, Basel, Switzerland Daha fazlası Daha az

Ozbey, U. | Attar, Rukset | Romero, M.A. | Alhewairini, S.S. | Afshar, B. | Sabitaliyevich, U.Y. | Farooqi, A.A.

Article | 2019 | Journal of Cellular Biochemistry120 ( 2 ) , pp.1060 - 1067

Wealth of information gleaned from decades of high-impact research work; scientists have disentangled the complicated web of versatile regulators that underlie cancer development and progression. Use of structural biology approaches and functional genomics have helped us to gain new insights into complex nature of cancer, and it is now clear that genetic/epigenetic mutations, overexpression of oncogenes, inactivation of tumor suppressors, loss of apoptosis, and versatility of protein binding partners have contributory roles in carcinogenesis and metastatic spread. It is becoming progressively more understandable that reprogramming o . . .f gene expression during and nontranscriptional changes during cancer development and progression are initiated and controlled by deregulated signal transduction cascades, all of which collectively create an incalculable complexity. Data obtained through preclinical and clinical trials revealed that alterations in the targeted oncogenes and other downstream, and parallel pathways played a central role in the development of resistance against different therapeutics. Phytochemicals have regained limelight, and different natural products are currently being tested for efficacy in preclinical studies. Apigenin, a plant-derived flavonoid has considerable pharmacological value and is reportedly involved in the regulation of different signaling cascades. In this review, we have attempted to summarize rapidly evolving understanding of molecular biologists and pharmacologists about the potential of apigenin in the regulation of deregulated signaling pathways in different cancers. We have emphasized on the regulation of WNT/ß-catenin and janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. We also comprehensively discuss how apigenin restored apoptosis in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant cancers. The review also gives a snapshot of microRNAs (miRNAs) that regulate wide-ranging biological processes, and it is now clear that each miRNA can control hundreds of gene targets. Apigenin was noted to upregulate miR-520b and miR-101 in different cancers to inhibit tumor growth. Moreover, apigenin-induced apoptotic rate was significantly higher when used in combination with miR-423-5p inhibitors or miR-138 mimics. Better comprehension of linear and integrated signaling pathways will be helpful in effective therapeutic targeting of deregulated signaling pathways to inhibit/prevent cancer. © 2018 Wiley Periodicals, Inc Daha fazlası Daha az

Butt, G. | Shahwar, D. | Qureshi, M.Z. | Attar, Rukset | Akram, M. | Birinci, Y. | Farooqi, A.A.

Book Part | 2019 | Advances in Experimental Medicine and Biology1152 , pp.283 - 292

Based on the insights gleaned from decades of research, it seems clear that mechanistic target of rapamycin (mTOR) is an essential signaling node that integrates environmental clues for regulation of cell survival, metabolism and proliferation of the cells. However, overwhelmingly increasing scientific evidence has added a new layer of intricacy to already complicated and versatile signaling pathway of mTOR. Deregulation of spatio-temporally controlled mTOR-driven pathway played contributory role in breast cancer development and progression. Pharmacologists and molecular biologists have specifically emphasized on the identification . . .and development of mTOR-pathway inhibitors. In this chapter we have attempted to provide an overview of the most recent findings related to therapeutic targeting of mTOR-associated mTORC1 and mTORC2 in breast cancer. We have also comprehensively summarized regulation of mTOR and its partners by microRNAs in breast cancer. © 2019, Springer Nature Switzerland AG Daha fazlası Daha az

Qureshi, M.Z. | Attar, Rukset | Romero, M.A. | Sabitaliyevich, U.Y. | Nurmurzayevich, S.B. | Ozturk, O. | Farooqi, A.A.

Article | 2019 | Journal of Cellular Biochemistry120 ( 8 ) , pp.12091 - 12100

Entry of ß-elemene into various phases of clinical trials advocates its significance as a premium candidate likely to gain access to mainstream medicine. Based on the insights gleaned from decades of research, it seems increasingly transparent that ß-elemene has shown significant ability to modulate multiple cell signaling pathways in different cancers. We partition this multicomponent review into how ß-elemene strategically modulates various signal transduction cascades. We have individually summarized regulation of tumor necrosis factor related apoptosis-inducing ligand, signal transducers and activators of transcription, transfor . . .ming growth factor/SMAD, NOTCH, and mammalian target of rapamycin pathways by ß-elemene. Last, we will discuss the results of clinical trials of ß-elemene and how effectively we can use these findings to stratify patients who can benefit most from ß-elemene. © 2019 Wiley Periodicals, Inc Daha fazlası Daha az

Fayyaz, S. | Qureshi, M.Z. | Alhewairini, S.S. | Avnioglu, S. | Attar, Rukset | Sabitaliyevich, U.Y. | Pawlak-Adamska, E.

Article | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 7 ) , pp.15 - 20

Ampelopsin or Dihydromyricetin is gradually emerging as a high-quality natural product because of its ability to modulate wide-ranging signaling pathways. Ampelopsin (Dihydromyricetin) has been reported to effectively modulate growth factor receptor (VEGFR2 and PDGFRß) mediated signaling,  TRAIL/TRAIL-R pathway, JAK/STAT and mTOR-driven signaling in different cancers. Ampelopsin (Dihydromyricetin) has also been shown to exert inhibitory effects on the versatile regulators which trigger EMT (Epithelial-to-Mesenchymal Transition). Findings obtained from in-vitro studies are encouraging and there is a need to comprehensively analyze ho . . .w Ampelopsin (Dihydromyricetin) inhibits tumor growth in different cancer models. Better knowledge of efficacy of Ampelopsin (Dihydromyricetin) in tumor bearing mice will be helpful in maximizing its translational potential Daha fazlası Daha az

Farooqi, A.A. | Attar, Rukset | Bageshlooyafshar, B. | Sabitaliyevich, U.Y. | Nurmurzayevich, S.B. | Yelekenova, A.B. | Gormus, U.

Review | 2019 | Cellular and molecular biology (Noisy-le-Grand, France)65 ( 3 ) , pp.72 - 75

Kisspeptin-driven intracellular signaling has captured enormous attention because of its central role in cancer onset and progression. Wealth of information has helped us to develop a better understanding of the critical roles of Kisspeptin-mediated signaling in different cancers. However, astonishingly, we have not yet drilled down deep into the mysterious aspects associated with non-coding RNA mediated regulation of Kisspeptin-driven signaling. Therefore, in this mini-review, we will comprehensively analyze available evidence related to miRNAs and long non-coding RNAs (LncRNAs) and their ability to modulate Kisspeptin-mediated sig . . .naling. There are visible knowledge gaps about interplay between non-coding RNAs and Kisspeptin-mediated signaling. It will be appropriate to say that we have just started to scratch the surface of an entirely new regulatory layer of Kisspeptin-mediated transduction cascade. Mechanistically, it has been revealed that inhibition of Kisspeptin mediated signaling activated and stimulated the entry of NF?B into the nucleus to stimulate expression of proteins which can sequentially inactivate tumor suppressor miRNAs. miRNAs have also an instrumental role in regulation of proteins which post-translationally modify and inhibit KISS1 expression. It is becoming progressively more understandable that LncRNAs act as miRNA sponges and protect oncogenic mRNAs. However, these facets are also incompletely investigated. Identification of LncRNAs which interfere with Kisspeptin-mediated pathway either through acting as miRNA sponges or working with methylation-associated machinery will be helpful in sharpening the resolution of the pixels of the regulatory network which shapes Kisspeptin-mediated signaling Daha fazlası Daha az

Fayyaz, S. | Javed, Z. | Attar, Rukset | Farooqi, A.A. | Yaylim, I. | Ahmad, A.

Review | 2019 | Seminars in Cancer Biology58 , pp.56 - 64

Large-scale sequencing methodologies have helped us identify numerous genomic alterations and we have started to scratch the surface of many new targets for treatment of cancer and the associated predictive biomarkers. TRAIL (TNF-related apoptosis-inducing ligand) is a highly appreciated anti-cancer molecule because of its ability to selectively target cancer cells. However, confluence of information suggests that cancer cells develop resistance against TRAIL-based therapeutics. It is being realized that overexpression of anti-apoptotic proteins and inactivation of pro-apoptotic proteins significantly impairs TRAIL triggered apoptos . . .is, particularly in clinical settings. Re-balancing of pro-and anti-apoptotic proteins and upregulation of death receptors with functionally active extrinsic and intrinsic apoptotic pathways are necessary to sensitize cancer cells to TRAIL based therapeutics. microRNAs (miRNAs) are involved in regulation of myriad of molecular processes and characterized into oncogenic and tumor suppressor miRNAs. Accumulating data has identified miRNAs which positively or negatively regulate TRAIL mediated signaling in cancer cells, helping us understand different steps at which TRAIL-mediated apoptotic signaling can be targeted. Here, we assess the status of our understanding of the mechanisms related to miRNA regulation of TRAIL mediated signaling, as well as the existing gaps therein, and discuss the challenges and opportunities that will help us get closer to personalized medicine. © 2019 Elsevier Lt Daha fazlası Daha az