scholarly journals The Potential of MiRNAs as Biomarkers and Therapy Targets for Cancer

2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Teresa L. Wargasetia

MicroRNAs (miRNAs) are involved in the signaling circuits regulation within a cell andtheir deregulation plays an important role in cancer development and progression. In thisreview, we discussed miRNA biogenesis, miRNA function and the effect of miRNA abnormalitiesin cellular pathways that led to transformation of normal cells into cancer cells, as well as theindication of miRNAs as diagnostic and prognostic biomarkers of various types of cancer, asbiomarkers to predict the response to cancer therapy and the potential for development ofmiRNAs as cancer targeted therapy.Keywords: miRNA, cancer, diagnostic biomarker, prognostic biomarker, cancer therapy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jinliang Gao ◽  
Tao Luo ◽  
Jinke Wang

AbstractAlthough some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we develop a ferroptosis-based therapy by combining iron nanoparticles and cancer-specific gene interference. The expression of two iron metabolic genes (FPN and LCN2) was selectively knocked down in cancer cells by Cas13a or microRNA controlled by a NF-κB-specific promoter. Cells were simultaneously treated by iron nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells. However, the same treatment had little effect on normal cells. By transferring genes with adeno-associated virus and iron nanoparticles, the significant tumor growth inhibition and durable cure were obtained in mice with the therapy. In this work, we thus show a cancer therapy based on gene interference-enhanced ferroptosis.


2015 ◽  
Author(s):  
Michael D. Forrest

ABSTRACTI use the Nernst equation, parameterised with experimental data, to predict that cancer cells will accumulate more of a lipophilic anion than normal cells. This effect is correlated to charge number. Model cancer cells accumulate *100 more of an anion, *103 more di-anion, *106 more tri-anion, *108 more tetra-anion and *1010 more penta-anion (>>1 billion times more). The trend endures, conveying even greater specificity, for higher charge numbers. This effect could be leveraged for cancer therapy. Wherein the lipophilic anion is a toxin that targets some vital cellular process, which normal and cancer cells may even share. It delivers a high, lethal dose to cancer cells but a low, safe dose to normal cells. This mathematical finding conveys the prospect of a broad, powerful new front against cancer.


Author(s):  
Anne-Marie Sapse

Cancer is an extraordinarily complicated group of diseases which are characterized by the loss of normal control of the maintenance of cellular organization in the tissues. It is still not completely understood how much of the disease is of genetic, viral, or environmental origin. The result, however, is that cancer cells possess growth advantages over normal cells, a reality which damages the host by local pressure effects, destruction of tissues, and secondary systemic effects. As such, a goal of cancer therapy is the destruction of cancer cells via chemotherapeutic agents or radiation. Since the late 1940s, when Farber treated leukemia with methotrexate, cancer therapy with cytotoxic drugs made enormous progress. Chemotherapy is usually integrated with other treatments such as surgery, radiotherapy, and immunotherapy, and it is clear that post-surgery, it is effective with solid tumors. This is due to the fact that only systemic therapy can attack micrometastases. The rationale for using chemotherapy is the control of tumor-cell populations via a killing mechanism. The major problem in this approach is the lack of selectivity of chemotherapeutic agents. Some agents indeed preferentially kill cancer cells, but no agents have been synthesized yet which kill only cancer cells and do not affect normal cells. Unfortunately, normal tissues are affected, giving rise to a multitude of side effects. In addition to drugs exhibiting cytotoxic activity, antiproliferative drugs are also formulated. According to their mode of action, anti-cancer drugs are divided into several classes. . . . alkylating agents antimetabolites DNA intercalators mitotic inhibitors lexitropsins drugs which bind covalently to DNA . . . Experimental studies of these molecules are complemented and enhanced by theoretical studies. Some of the theoretical studies use molecular mechanics methods while others apply ab initio or semi-empirical quantum-chemistry methods. Most of these molecules are large and besides their structures and properties it is important to investigate their interaction with DNA fragments (themselves large molecules). Ab initio calculations cannot always be applied to the whole system. Therefore, models are used and through a judicious choice of the entities investigated, the calculations can shed light on the problem and provide enough information to complement the experimental studies.


2020 ◽  
Vol 12 (15) ◽  
pp. 17276-17289
Author(s):  
Joanna Pilch ◽  
Edyta Matysiak-Brynda ◽  
Agata Kowalczyk ◽  
Piotr Bujak ◽  
Zofia Mazerska ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6684
Author(s):  
Samuele Lodovichi ◽  
Tiziana Cervelli ◽  
Achille Pellicioli ◽  
Alvaro Galli

Alterations in DNA repair pathways are one of the main drivers of cancer insurgence. Nevertheless, cancer cells are more susceptible to DNA damage than normal cells and they rely on specific functional repair pathways to survive. Thanks to advances in genome sequencing, we now have a better idea of which genes are mutated in specific cancers and this prompted the development of inhibitors targeting DNA repair players involved in pathways essential for cancer cells survival. Currently, the pivotal concept is that combining the inhibition of mechanisms on which cancer cells viability depends is the most promising way to treat tumorigenesis. Numerous inhibitors have been developed and for many of them, efficacy has been demonstrated either alone or in combination with chemo or radiotherapy. In this review, we will analyze the principal pathways involved in cell cycle checkpoint and DNA repair focusing on how their alterations could predispose to cancer, then we will explore the inhibitors developed or in development specifically targeting different proteins involved in each pathway, underscoring the rationale behind their usage and how their combination and/or exploitation as adjuvants to classic therapies could help in patients clinical outcome.


Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769222 ◽  
Author(s):  
Hossein Allahyari ◽  
Sahar Heidari ◽  
Mehdi Ghamgosha ◽  
Parvaneh Saffarian ◽  
Jafar Amani

Cancer is one of the main reasons of death in the most countries and in Iran. Immunotherapy quickly became one of the best methods of cancer treatment, along with chemotherapy and radiation. “Immunotoxin Therapy” is a promising way of cancer therapy that is mentioned in this field. Immunotoxins are made from a toxin attaching to an antibody target proteins present on cancer cells. The first-generation immunotoxins were made of a full-length toxin attached to whole monoclonal antibodies. But, these immunotoxins could bind to normal cells. DAB389IL2 was the first immunotoxin approved by the Food and Drug Administration. Current trends and researches are ongoing on finding proteins that in combination with immunotoxins have minimal immunogenicity and the most potency for target cell killing.


2009 ◽  
Vol 1185 ◽  
Author(s):  
Nan Iyer ◽  
Katelyn Cooper ◽  
Jianing Yang ◽  
Frederic Zenhausern

AbstractMeasuring elastic properties of cells has gained importance in the study of malignant transformations. The stiffness of a cell, which is technically referred to as the modulus of elasticity or Young's Modulus, E, is the measure of the amount of cell deformation caused by an applied known force. In vitro studies have shown that cancer cells have much lower elastic stiffness than normal cells. These stiffness measurements and their differences can be used to study the behavioral mechanics of how cancer cells grow, profligate, and die in a patient. Another important use of this difference in elasticity is in cancer detection.In this study, we explore the viability of measuring the elastic modulus of cancer cells by using a method that only requires the use of a low magnification microscope and a digital camera. In particular we are interested in applying the previously reported relationship between the wrinkling of thin films and the elastic properties of freely floating polystyrene (PS) films. Our work extends the scope of previous thin film studies by evaluating wrinkle formation in floating polystyrene films coated with biological cells. Our results show that the wrinkle formation is modified, both in morphology and in size, by the presence of a cellular monolayer on top of the PS film.


2011 ◽  
Vol 89 (4) ◽  
pp. 359-376 ◽  
Author(s):  
Marta Gladych ◽  
Aneta Wojtyla ◽  
Blazej Rubis

Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy. A correlation between short telomere length and increased mortality was revealed in many studies. The telomerase expression/activity appears to be one of the most crucial factors to study to improve cancer therapy and prevention. However, this multisubunit enzymatic complex can be regulated at various levels. Thus, several strategies have been proposed to control telomerase in cancer cells such as anti-sense technology against TR and TERT, ribozymes against TERT, anti-estrogens, progesterone, vitamin D, retinoic acid, quadruplex stabilizers, telomere and telomerase targeting agents, modulation of interaction with other proteins involved in the regulation of telomerase and telomeres, etc. However, the transcription control of key telomerase subunits seems to play the crucial role in whole complexes activity and cancer cells immortality. Thus, the research of telomerase regulation can bring significant insight into the knowledge concerning stem cells metabolism but also ageing. This review summarizes the current state of knowledge of numerous telomerase regulation mechanisms at the transcription level in human that might become attractive anti-cancer therapy targets.


2017 ◽  
Vol 5 (29) ◽  
pp. 5870-5880 ◽  
Author(s):  
Tilahun Ayane Debele ◽  
Kuan-Yi Lee ◽  
Ning-Yu Hsu ◽  
Yi-Ting Chiang ◽  
Lu-Yi Yu ◽  
...  

pH-Sensitive rod-like micelles were designed to improve drug release, to increase cytotoxicity towards cancer cells, and to reduce cytotoxicity towards normal cells.


2021 ◽  
Author(s):  
Rapeepun Soonnarong ◽  
Sucharat Tungsukruthai ◽  
Bodee Nutho ◽  
Thanyada Rungrotmongkol ◽  
Chanida Vinayanuwattikun ◽  
...  

Abstract Background: Metal oxide nanomaterials are increasingly being exploited in cancer therapy thanks to their unique properties, which can enhance the efficacy of current cancer therapies. However, the nanotoxicity and mechanism of Ti0.8O2 nanosheets for specific site-targeting strategies in NSCLC have not yet been investigated.Methods: The effects of Ti0.8O2 nanosheets on cytotoxicity in NSCLC cells and normal cells were examined. The apoptosis characteristics, including condensed and fragmented nuclei, as assessed by positive staining with annexin V. The cellular uptake of the nanosheets and the induction of stress fiber were assessed via transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses, respectively. We also evaluated the expression of protein in death mechanism to identify the molecular mechanisms behind the toxicity of these cells. We investigated the relationship between S-nitrosylation and the increase in p53 stability by molecular dynamics.Results: Ti0.8O2 nanosheets caused cytotoxicity in several lung cancer cells, but not in normal cells. The nanosheets could enter lung cancer cells and exert an apoptosis induction. Results for protein analysis further indicated the activation of p53, increased Bax, decreased Bcl-2 and Mcl-1, and activation of caspase-3. The nanosheets also exhibited a substantial apoptosis effect in drug-resistant metastatic primary lung cancer cells, and it was found that the potency of the nanosheets was dramatically higher than that of cisplatin and etoposide. In terms of their mechanism of action, we found that the mode of apoptosis induction was through the generation of cellular ONOO− mediated the S-nitrosylation of p53 at C182. Molecular dynamics analysis further showed that the S-nitrosylation of one C182 stabilized the p53 dimer. Consequently, this nitrosylation of the protein led to an upregulation of p53 through its stabilization.Conclusions: Taking all the evidence together, we provided information on the apoptosis induction effect of the nanosheets through a molecular mechanism involving reactive nitrogen species, which affects the protein stability; thus emphasizing the novel mechanism of action of nanomaterials for cancer therapy.


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