scholarly journals Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Yue Zhang ◽  
Huizhu Qian ◽  
Jing He ◽  
Wen Gao
Keyword(s):  
Cancer Treatment ◽  
Cancer Progression ◽  
Treatment Resistance ◽  
Cancer Drug ◽  
Cancer Drug Resistance ◽  
New Ideas ◽  
Proliferation And Metastasis ◽  
Trna Halves ◽  
Cell Proliferation And Metastasis

Abstract The tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are newly discovered noncoding RNAs in recent years. They are derived from specific cleavage of mature and pre-tRNAs and expressed in various cancers. They enhance cell proliferation and metastasis or inhibit cancer progression. Many studies have investigated their roles in the diagnosis, progression, metastasis, and prognosis of various cancers, but the mechanisms through which they are involved in resistance to cancer treatment are unclear. This review outlines the classification of tRFs and tiRNAs and their mechanisms in cancer drug resistance, thus providing new ideas for cancer treatment.

Quest of EMT and CSC

2019 ◽  
Author(s):  
Shihori Tanabe
Keyword(s):  
Drug Resistance ◽  
Stem Cell ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Therapeutics ◽  
Cancer Drug ◽  
Phenotypic Change ◽  
Mesenchymal Transition ◽  
Cancer Drug Resistance ◽  
The Relationship

Epithelial-mesenchymal transition (EMT), an important phenotypic change from epithelial to mesenchymal like cells, has the increasing impact for cancer progression in terms of the involvement in cancer stem cell (CSC). The EMT-featured cells and CSCs are important factors for the acquisition of cancer drug resistance. The understanding of EMT program activation is important for targeting CSCs in cancer therapy. The relationship between EMT and CSC in cancer therapeutics is focused in the editorial.

scholarly journals Exosomal miR-122-5p inhibits tumorigenicity of gastric cancer by downregulating GIT1

2021 ◽  
Vol 36 (1) ◽  
pp. 36-46
Author(s):  
Yigang Jiao ◽  
Li Zhang ◽  
Jun Li ◽  
Yuqi He ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Proliferation And Metastasis ◽  
Gastric Cancer Cell Proliferation ◽  
Gastric Cancer Progression ◽  
Cell Proliferation And Metastasis

Background: microRNAs (miRNAs) are non-coding RNAs with important roles in the progression of human cancers, including gastric cancer. Exosomes are extracellular vesicles, which could transfer numerous noncoding RNAs, such as miRNAs. Here, in our study, we intended to investigate the role of exosomal miR-122-5p in gastric cancer progression. Methods: Exosomes were isolated utilizing commercial kit or ultracentrifugation. Biomarkers of exosomes or epithelia-mesenchymal transition (EMT) were monitored by western blot. Expression levels of miR-122-5p and G-protein-coupled receptor kinase interacting protein-1 ( GIT1) were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation and apoptosis were assessed by colony formation assay, methyl thiazolyl tetrazolium assay and flow cytometry. Cell metastasis was evaluated via Transwell assay. The interaction between miR-122-5p and GIT1 was validated by dual-luciferase reporter assay. Furthermore, tumor growth in vivo was detected by xenograft assay. Results: Exosomes were successfully isolated. MiR-122-5p was downregulated in exosomes derived from the serum of gastric cancer patients. Exosomal miR-122-5p could hinder gastric cancer cell proliferation and metastasis in vitro and tumor growth in vivo. Knockdown of GIT1 also inhibited gastric cancer cell proliferation and metastasis. Exosomal miR-122-5p targeted GIT1 to alter cellular behaviors of gastric cancer cells. Conclusion: Exosomal miR-122-5p suppressed gastric cancer progression by targeting GIT1.

scholarly journals SPOCK1 promotes breast cancer progression via interacting with SIX1 and activating AKT/mTOR signaling pathway

2019 ◽  
Author(s):  
Ming Xu ◽  
Xianglan Zhang ◽  
Songnan Zhang ◽  
Junjie Piao ◽  
Yang Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Histological Grade ◽  
Mtor Pathway ◽  
Clinical Prognosis ◽  
Mesenchymal Transition ◽  
Proliferation And Metastasis ◽  
Cell Proliferation And Metastasis

ABSTRACTSPOCK1 is highly expressed in many types of cancer, which has been recognized as a promoter of cancer progression, while its regulatory mechanism remains to be clear in breast cancer (BC). This study aimed to explore the precise function of SPOCK1 in BC progression and the mechanism by which SPOCK1 was involved in cell proliferation and epithelial-mesenchymal transition (EMT). Immunohistochemistry (IHC) and database analysis displayed that high expression of SPOCK1 was positively associated with histological grade, lymph node metastasis (LN) and poor clinical prognosis in BC. A series of assays both in vitro and in vivo elucidated that altering SPOCK1 level led to distinctly changes in BC cell proliferation and metastasis. Investigations of potential mechanisms revealed that SPOCK1 interacted with SIX1 could enhance cell proliferation, cell cycle and EMT process by activating the AKT/mTOR pathway, whereas inhibition of AKT/mTOR pathway or depletion of SIX1 reversed the effects of SPOCK1 overexpression. Furthermore, SPOCK1 and SIX1 were highly expressed in BC and might indicate poor prognoses. Altogether, SPOCK1/SIX1 promoted BC progression by activating AKT/mTOR pathway to accelerate cell proliferation and metastasis in BC, and SPOCK1/SIX1 might be promising clinical therapeutic targets to prevent BC progression.IMPORTANCEThe incidence of BC is alarmingly high and many patients initially diagnosed without detectable metastases will eventually develop metastatic lesions. The occurrence of metastasis is responsible for the death of many patients, which also represents a big challenge for researchers to improve the survival rates of BC patients. Hence the scientific community pays more attention on cancer targeted therapy. This research is significant for identifying the underlying mechanisms and capabilities of SPOCK1-induced BC activities, which will greatly apply novel targets and new treatment strategies for clinicians, leading to broader biomedical impacts.

scholarly journals Aberrant alternative splicing in breast cancer

2019 ◽  
Vol 11 (10) ◽  
pp. 920-929 ◽  
Author(s):  
Quan Yang ◽  
Jinyao Zhao ◽  
Wenjing Zhang ◽  
Dan Chen ◽  
Yang Wang
Keyword(s):  
Breast Cancer ◽  
Alternative Splicing ◽  
Cancer Progression ◽  
Gene Expression Regulation ◽  
Cancer Therapeutics ◽  
Cancer Drug ◽  
Splicing Factors ◽  
Cancer Drug Resistance ◽  
The Relationship

Abstract Alternative splicing is critical for human gene expression regulation, which plays a determined role in expanding the diversity of functional proteins. Importantly, alternative splicing is a hallmark of cancer and a potential target for cancer therapeutics. Based on the statistical data, breast cancer is one of the top leading causes of cancer-related deaths in women worldwide. Strikingly, alternative splicing is closely associated with breast cancer development. Here, we seek to provide a general review of the relationship between alternative splicing and breast cancer. We introduce the process of alternative splicing and its regulatory role in cancers. In addition, we highlight the functions of aberrant alternative splicing and mutations of splicing factors in breast cancer progression. Moreover, we discuss the role of alternative splicing in cancer drug resistance and the potential of being targets for cancer therapeutics.

scholarly journals New Perspectives of CYP1B1 Inhibitors in the Light of Molecular Studies

Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 817
Author(s):  
Renata Mikstacka ◽  
Zbigniew Dutkiewicz
Keyword(s):  
Cancer Progression ◽  
Cancer Chemoprevention ◽  
Cancer Drug ◽  
Cellular Functions ◽  
Cytochrome P450 1B1 ◽  
Cancer Drug Resistance ◽  
Human Cytochrome ◽  
Anti Cancer ◽  
Endogenous Substrates ◽  
Metabolism Of Xenobiotics

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic heme-containing monooxygenase. CYP1B1 contributes to the oxidative metabolism of xenobiotics, drugs, and endogenous substrates like melatonin, fatty acids, steroid hormones, and retinoids, which are involved in diverse critical cellular functions. CYP1B1 plays an important role in the pathogenesis of cardiovascular diseases, hormone-related cancers and is responsible for anti-cancer drug resistance. Inhibition of CYP1B1 activity is considered as an approach in cancer chemoprevention and cancer chemotherapy. CYP1B1 can activate anti-cancer prodrugs in tumor cells which display overexpression of CYP1B1 in comparison to normal cells. CYP1B1 involvement in carcinogenesis and cancer progression encourages investigation of CYP1B1 interactions with its ligands: substrates and inhibitors. Computational methods, with a simulation of molecular dynamics (MD), allow the observation of molecular interactions at the binding site of CYP1B1, which are essential in relation to the enzyme’s functions.

scholarly journals HES5 Activates Long Noncoding RNA UCA1 to Induce Colorectal Cancer Progression by Modulating miR-185/NOTCH3 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Mingming Wang ◽  
Qinlin Zheng ◽  
Zhengfei Zhao ◽  
Hong Deng ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Inhibitory Effect ◽  
Tumor Stages ◽  
Proliferation And Metastasis ◽  
Direct Target ◽  
Colorectal Cancer Progression ◽  
Cell Proliferation And Metastasis

Colorectal cancer (CRC) is one of the most common diagnosed cancers around the world. The poor prognosis and high fatality caused by metastasis are still the challenges for clinical treatment. Therefore, it is promising to clarify the detailed molecular mechanism of CRC metastasis. Accumulating evidences indicate that long noncoding RNAs (lncRNAs) play important roles in cancer progression including CRC. In this study, the function of lncRNA UCA1 was investigated. UCA1 was confirmed to be highly expressed in colorectal cancer. Moreover, the UCA1 expression level was positively related to tumor stages. Silencing UCA1 showed inhibitory effect on cell proliferation and metastasis. Both UCA1 and NOTCH3 were validated as direct targets of miR-185. Silencing UCA1 repressed NOTCH3 expression through the miR-185 sponge. NOTCH3 was found to be highly expressed in CRC patients and positively related to UCA1 expression. Furthermore, HES5 was verified as a transcription factor of UCA1, which induced UCA1 expression. In conclusion, UCA1 is a direct target of HES5. UCA1 promotes CRC metastasis through regulating the miR-185/NOTCH3 axis.

scholarly journals The interplay between m6A RNA methylation and noncoding RNA in cancer

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuai Ma ◽  
Chen Chen ◽  
Xiang Ji ◽  
Jinbo Liu ◽  
Quanbo Zhou ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Stem Cell Differentiation ◽  
Biological Functions ◽  
Rna Modifications ◽  
Proliferation And Metastasis ◽  
M6a Rna Methylation ◽  
Cell Proliferation And Metastasis

AbstractN6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested that m6A modification can affect the complexity of cancer progression by regulating biological functions related to cancer. M6A modification of noncoding RNAs regulates the cleavage, transport, stability, and degradation of noncoding RNAs themselves. It also regulates cell proliferation and metastasis, stem cell differentiation, and homeostasis in cancer by affecting the biological function of cells. Interestingly, noncoding RNAs also play significant roles in regulating these m6A modifications. Additionally, it is becoming increasingly clear that m6A and noncoding RNAs potentially contribute to the clinical application of cancer treatment. In this review, we summarize the effect of the interactions between m6A modifications and noncoding RNAs on the biological functions involved in cancer progression. In particular, we discuss the role of m6A and noncoding RNAs as possible potential biomarkers and therapeutic targets in the treatment of cancers.

scholarly journals MiR-124-3p/ZC3H15 Regulates Gastric Cancer Progression by Blocking FBXW7 Mediated Degradation of c-Myc

2020 ◽  
Author(s):  
Jianbing Hou ◽  
Yudong Liu ◽  
Du Yan ◽  
Pan Huang ◽  
Zhongze Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Biological Role ◽  
Potential Biomarker ◽  
Proliferation And Metastasis ◽  
Gastric Cancer Progression ◽  
Cell Proliferation And Metastasis

Abstract BACKGROUND: Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved eukaryotic protein, was involved in tumorigenesis and may be a potential biomarker in hepatocellular carcinoma (HCC) and acute myeloid leukemia (AML). However, the biological role of ZC3H15 in gastric cancer (GC) is unclear.METHODS: The potential correlation between ZC3H15 expression and GC prognosis was assessed based on the patient data analysis. The biological role of ZC3H15 in regulating cell proliferation and metastasis was evaluated in vitro and in vivo. In addition, the potential mechanism of ZC3H15 was investigated. RESULTS: we found that ZC3H15 expression was positively correlated with GC progression, including cell growth, metastasis and cancerogenesis. Through further investigations, we found that ZC3H15 could modulate c-Myc protein stability via suppressing the transcription of FBXW7, which was mainly responsible for c-Myc degradation. In addition, we revealed that miR-124-3p, a tumor suppressor of GC, was negatively associated with ZC3H15. We revealed that miR-124-3p was a critical upstream modulator of ZC3H15 in GC.CONCLUSIONS: Taken together, our studies unearth the important roles of ZC3H15 in GC development and suggest that miR-124-3p/ZC3H15/c-Myc axis may be a potential target for the treatment of GC.

Anticancer Activity of Diosgenin and its Semi-synthetic Derivatives: Role in Autophagy Mediated Cell Death and Induction of Apoptosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Bharat Goel ◽  
Shreyans K. Jain
Keyword(s):  
Cell Death ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Rational Approach ◽  
Potential Candidate ◽  
Potential Implication ◽  
Apoptosis Protein ◽  
Synthetic Derivatives

: During cancer progression, the unrestricted proliferation of cells is supported by the impaired cell death response provoked by certain oncogenes. Both autophagy and apoptosis are the signaling pathways of cell death, which are targeted for cancer treatment. Defects in apoptosis result in reduced cell death and ultimately tumor progression. The tumor cells lacking apoptosis phenomena are killed by ROS- mediated autophagy. The autophagic programmed cell death requires apoptosis protein for inhibiting tumor growth; thus, the interconnection between these two pathways determines the fate of a cell. The cross-regulation of autophagy and apoptosis is an important aspect to modulate autophagy, apoptosis and to sensibilise apoptosis-resistant tumor cells under metabolic stress and might be a rational approach for drug designing strategy for the treatment of cancer. Numerous proteins involved in autophagy have been investigated as the druggable target for anticancer therapy. Several compounds of natural origin have been reported, to control autophagy activity through the PI3K/Akt/mTOR key pathway. Diosgenin, a steroidal sapogenin has emerged as a potential candidate for cancer treatment. It induces ROS-mediated autophagy, inhibits PI3K/Akt/mTOR pathway, and produces cytotoxicity selectively in cancer cells. This review aims to focus on optimal strategies using diosgenin to induce apoptosis by modulating the pathways involved in autophagy regulation and its potential implication in the treatment of various cancer. The discussion has been extended to the medicinal chemistry of semi-synthetic derivatives of diosgenin exhibiting anticancer activity.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

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