Department Of Human Genetics And Molecular Medicine

Permanent URI for this communityhttps://kr.cup.edu.in/handle/32116/103

Browse

Subject: search.filters.subject.Cancer

Search Results

Now showing 1 - 10 of 12
  • No Thumbnail Available
    Item
    Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis
    (Springer Science and Business Media Deutschland GmbH, 2022-11-28T00:00:00) Tuli, Hardeep Singh; Kaur, Jagjit; Vashishth, Kanupriya; Sak, Katrin; Sharma, Ujjawal; Choudhary, Renuka; Behl, Tapan; Singh, Tejveer; Sharma, Sheetu; Saini, Adesh K.; Dhama, Kuldeep; Varol, Mehmet; Sethi, Gautam
    ROS include hydroxyl radicals (HO.), superoxide (O2.), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
  • No Thumbnail Available
    Item
    Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs
    (Academic Press, 2022-10-28T00:00:00) Sharma, Uttam; Tuli, Hardeep Singh; Uttam, Vivek; Choudhary, Renuka; Sharma, Bunty; Sharma, Ujjawal; Prakash, Hridayesh; Jain, Aklank
    Despite advanced clinical and translational oncology research, mortality rates are still increasing worldwide. Recently, a class of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been well investigated in regulating biological, molecular, and cellular signaling pathways. This review article provided the current research progress on how miRNAs, lncRNAs, and circRNAs regulate Hedgehog (Hh) and Hippo signaling pathways in various cancers. These ncRNAs target both pathways' key downstream molecules and may be used for targeted cancer treatment. Moreover, Hh and Hippo signaling pathways crosstalked with each other through Gli1 of Hh pathways and YAP1/TEAD molecules of Hippo pathways during cancer progression. Additionally, Hh and Hippo signaling pathways regulate resistance against the chemo, radio, and immune therapies for several types of cancer via inducing GLI and YAP/TAZ proteins level. Therefore, to improve the treatment regime, we presented the role of various prominent phytochemicals such as curcumin, resveratrol, genistein, quercetin, paclitaxel, and silibinin in regulating lncRNAs, miRNAs, circRNA through Hedgehog and Hippo signaling pathways� constituents in cancers. We believe that knowledge obtained from this review may help make new drugs for cancer treatment in the future. � 2022 Elsevier Ltd
  • No Thumbnail Available
    Item
    Targeting Redox Homeostasis of Tumor Cells by Therapeutic Compounds in Cancer: An Indian Perspective
    (Springer Singapore, 2022-09-28T00:00:00) Vasudeva, Kanika; Chaturvedi, Pragya; Khan, Rahul; Sahu, Prachi; Munshi, Anjana
    Cancer is one of the significant causes of morbidity and mortality in the world. The role of oxidative stress in tumor progression and metastasis has been under focus since the last two decades, suggesting the importance of redox balance upon which cancer cells thrive to promote oncogenic phenotype. Therefore, it is highly warranted to develop therapies that can disrupt the fine-tuned intracellular reactive oxygen species (ROS) balance of tumor cells. Even though classical chemotherapy, radiotherapy, and many FDA-approved chemotherapeutic drugs modulate ROS levels, the associated side effects make it worthwhile to explore alternative options. Various compounds of natural origin have high efficacy and minimum side effects and pose a low risk of recurrence. This chapter has been compiled to give a thorough account of medicinal plants of Indian origin that have been implicated in ROS modulation and their potential applications in clinical settings. � Springer Nature Singapore Pte Ltd. 2022.
  • No Thumbnail Available
    Item
    Differential molecular mechanistic behavior of HDACs in cancer progression
    (Springer, 2022-08-16T00:00:00) Singh, Tashvinder; Kaur, Prabhsimran; Singh, Paramdeep; Singh, Sandeep; Munshi, Anjana
    Genetic aberration including mutation in oncogenes and tumor suppressor genes transforms normal cells into tumor cells. Epigenetic modifications work concertedly with genetic factors in controlling cancer development. Histone acetyltransferases (HATs), histone deacetylases (HDACs), DNA methyltransferases (DNMTs) and chromatin structure modifier are prospective epigenetic regulators. Specifically, HDACs are histone modifiers regulating the expression of genes implicated in cell survival, growth, apoptosis, and metabolism. The majority of HDACs are highly upregulated in cancer, whereas some have a varied function and expression in cancer progression. Distinct HDACs have a positive and negative role in controlling cancer progression. HDACs are also significantly involved in tumor cells acquiring metastatic and angiogenic potential in order to withstand the anti-tumor microenvironment. HDACs� role in modulating metabolic genes has also been associated with tumor development and survival. This review highlights and discusses the molecular mechanisms of HDACs by which they regulate cell survival, apoptosis, metastasis, invasion, stemness potential, angiogenesis, and epithelial to mesenchymal transitions (EMT) in tumor cells. HDACs are the potential target for anti-cancer drug development and various inhibitors have been developed and FDA approved for a variety of cancers. The primary HDAC inhibitors with proven anti-cancer efficacy have also been highlighted in this review. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
  • No Thumbnail Available
    Item
    Long non-coding RNAs involved in different steps of cancer metastasis
    (Springer Science and Business Media Deutschland GmbH, 2022-02-04T00:00:00) Suman, P.; Chhichholiya, Y.; Kaur, P.; Ghosh, S.; Munshi, A.
    Non-proteincoding transcripts bearing 200 base pairs known as long non-coding RNAs (lncRNAs) play a role in a variety of molecular mechanisms, including cell differentiation, apoptosis and metastasis. Previous studies have suggested that frequently dysregulated lncRNAs play a crucial role in various aspects of cancer metastasis. Metastasis is the main leading cause of death in cancer. The role of lncRNAs in different stages of metastasis is the subject of this review. Based on in vitro and in vivo investigations on metastasis, we categorized lncRNAs into distinct stages of metastasis including angiogenesis, invasion, intravasation, survival in circulation, and extravasation. The involvement of lncRNAs in angiogenesis and invasion has been extensively studied. Here, we comprehensively discuss the role and functions of these lncRNAs with a particular focus on the molecular mechanisms. � 2022, The Author(s), under exclusive licence to Federaci�n de Sociedades Espa�olas de Oncolog�a (FESEO).
  • No Thumbnail Available
    Item
    Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4
    (BioMed Central Ltd, 2021-11-27T00:00:00) Sharma, Praveen; Sharma, Vibhuti; Ahluwalia, Tarunveer Singh; Dogra, Nilambra; Kumar, Santosh; Singh, Sandeep
    Background and objectives: MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria. Methods and results: Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells. Conclusion: These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription. � 2021, The Author(s).
  • No Thumbnail Available
    Item
    Design, Synthesis and Biological Evaluation of New 5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles as Topoisomerase Inhibitors
    (John Wiley and Sons Inc, 2021-07-09T00:00:00) Kaur, Manpreet; Mehta, Vikrant; Arora, Sahil; Munshi, Anjana; Singh, Sandeep; Kumar, Raj
    5-(2-Nitrophenyl)-1-aryl-1H-pyrazoles are designed as topoisomerase (Topo) inhibitors, synthesised and assessed for their anticancer properties against breast (MDA-MB-231 and MCF7), lung (A549), and colorectal (HCT116) cancer cell lines. All the compounds induced significant cytotoxicity at low micromolar concentration. The compound 5e exerted potential anticancer effects on breast cancer cell lines at a low micromolar level (IC50<2 ?M), and showed negligible toxicity towards normal cells. Compound 5 e reduced reactive oxygen species (ROS) level in breast cancer cells, altered mitochondrial membrane potential and induced the cell cycle arrest at the G2/M phase. This was accompanied by downregulation of oncogenic p-Akt and upregulation of p-PTEN along with modulation of apoptotic markers suggesting multiple mechanisms to reduce cancer cell viability. Finally, the topoisomerase inhibition assay revealed the inhibitory activity of 5 e against Topo I and Topo II. � 2021 Wiley-VCH GmbH.
  • No Thumbnail Available
    Item
    Obesity-Induced Chronic Low-Level Inflammation and Cancers
    (Springer Singapore, 2021-07-18T00:00:00) Bhattacharya, Neetu; Maurya, Shashank Kumar; Bhattacharya, Amit; Senapati, Sabyasachi
    The World Health Organization (WHO) has highlighted �overweight and obesity� as a public health concern and a significant risk factor for several chronic diseases, including diabetes, cardiovascular diseases, and cancers. The association between the different factors that can lead to the chronic inflammatory condition in the obese persons and their effect in tumorigenesis and several cancers (esophageal, liver, colon, postmenopausal breast, and endometrial cancers) have been partially unraveled. The functional association between inflammation and cancer is not new. Existing hypotheses of obesity-associated cancer underline direct effects of dietary ingredients or metabolic imbalance in the body. The recent evidences suggest a significant connection between chronic inflammation and cancer risk, possibly involving dietary and metabolic components. In the nineteenth century, Virchow first addressed the involvement of immune cells in tumorigenesis (Balkwill and Mantovani, The Lancet 357:539�545, 2001). The mediators and cellular effectors of inflammation are essential components of the tumor microenvironment and are more likely to contribute to tumor growth, its development and immunosuppression (Coussens and Werb, Nature 420:860�867, 2002). A strong relationship of chronic inflammation with malignant diseases can be traced in several individuals with inflammatory bowel diseases, such as Ulcerative colitis and Crohn�s disease, also developing colon carcinogenesis. Further, hepatitis C infection in the hepatic cells has been predisposed to liver carcinoma. Understanding these molecular pathways of cancer-related inflammation could lead to identification of new target molecules for improved diagnosis and treatment regimes. In this chapter, we will critically discuss the roles of cytokines, chemokines, growth factors, and inflammatory signaling pathways related to obesity and cancer risk. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.
  • No Thumbnail Available
    Item
    Small regulatory molecules acting big in cancer: Potential role of mito-miRs in cancer
    (Bentham Science Publishers, 2019) Sharma P.; Bharat; Dogra N.; Singh S.
    MicroRNAs [miRNAs] are short, non-coding, single stranded RNA molecules regulating gene expression of their targets at the posttranscriptional level by either degrading mRNA or by inhibiting translation. Previously, miRNAs have been reported to be present inside the mitochondria and these miRNAs have been termed as mito-miRs. Origin of these mito-miRs may either be from mitochondrial genome or import from nucleus. The second class of mito-miRs makes it important to unravel the involvement of miRNAs in crosstalk between nucleus and mitochondria. Since miRNAs are involved in various physiological processes, their deregulation is often associated with disease progression, including cancer. The current review focuses on the involvement of miRNAs in different mitochondrial mediated processes. It also highlights the importance of exploring the interaction of miRNAs with mitochondrial genome, which may lead to the development of small regulatory RNA based therapeutic options.
  • Thumbnail Image
    Item
    Potential Mitochondrial-Specific Function Of piRNAs
    (Central University of Punjab, 2018) Paul, Shouvik; Singh, Sandeep
    Piwi-interacting RNAs (piRNAs) are (26-31 nt) small noncoding RNAs processed from their longer precursor transcripts with the help of Piwi proteins. There are more than 30,000 piRNA genes present in the human genome which now turns out to be emerging player in both homeostasis and diseases. Localization of piRNA and PIWI in the repeat region of the mammalian nuclear genome in germ cells has been reported, although localization and potential functional role of piRNA in the mammalian mitochondrial genome are largely unknown. We have taken 111 piRNA sequences found in the MCF-7 mitochondrial genome, which is obtained by NGS analysis for alignment study. Resulting piRNA have been aligned with DQ112870 North American Homo sapiens mitochondrion genome for studying post- transcriptional roles of piRNA.