Curcumin inhibits cancer progression through regulating expression of microRNAs

Curcumin, a major yellow pigment and spice in turmeric and curry, is a powerful anti-cancer agent. The anti-tumor activities of curcumin include inhibition of tumor proliferation, angiogenesis, invasion and metastasis, induction of tumor apoptosis, increase of chemotherapy sensitivity, and regulation of cell cycle and cancer stem cell, indicating that curcumin maybe a strong therapeutic potential through modulating various cancer progression. It has been reported that microRNAs as small noncoding RNA molecules are related to cancer progression, which can be regulated by curcumin. Dysregulated microRNAs play vital roles in tumor biology via regulating expressions of target genes and then influencing multiple cancer-related signaling pathways. In this review, we focused on the inhibition effect of curcumin on various cancer progression by regulating expression of multiple microRNAs. Curcumin-induced dysregulation of microRNAs may activate or inactivate a set of signaling pathways, such as Akt, Bcl-2, PTEN, p53, Notch, and Erbb signaling pathways. A better understanding of the relation between curcumin and microRNAs may provide a potential therapeutic target for various cancers.

Download Full-text

Sulforaphane Inhibits the Expression of Long Noncoding RNA H19 and Its Target APOBEC3G and Thereby Pancreatic Cancer Progression

Cancers ◽

10.3390/cancers13040827 ◽

2021 ◽

Vol 13 (4) ◽

pp. 827

Author(s):

Yiqiao Luo ◽

Bin Yan ◽

Li Liu ◽

Libo Yin ◽

Huihui Ji ◽

...

Keyword(s):

Cancer Progression ◽

Colony Formation ◽

Noncoding Rna ◽

Target Genes ◽

Gene Array ◽

New Drugs ◽

Tumor Promoter ◽

Ductal Adenocarcinoma ◽

Pilot Studies

Pancreatic ductal adenocarcinoma (PDAC) is extremely malignant and the therapeutic options available usually have little impact on survival. Great hope is placed on new therapeutic targets, including long noncoding RNAs (lncRNAs), and on the development of new drugs, based on e.g., broccoli-derived sulforaphane, which meanwhile has shown promise in pilot studies in patients. We examined whether sulforaphane interferes with lncRNA signaling and analyzed five PDAC and two nonmalignant cell lines, patient tissues (n = 30), and online patient data (n = 350). RT-qPCR, Western blotting, MTT, colony formation, transwell and wound healing assays; gene array analysis; bioinformatics; in situ hybridization; immunohistochemistry and xenotransplantation were used. Sulforaphane regulated the expression of all of five examined lncRNAs, but basal expression, biological function and inhibition of H19 were of highest significance. H19 siRNA prevented colony formation, migration, invasion and Smad2 phosphorylation. We identified 103 common sulforaphane- and H19-related target genes and focused to the virus-induced tumor promoter APOBEC3G. APOBEC3G siRNA mimicked the previously observed H19 and sulforaphane effects. In vivo, sulforaphane- or H19 or APOBEC3G siRNAs led to significantly smaller tumor xenografts with reduced expression of Ki67, APOBEC3G and phospho-Smad2. Together, we identified APOBEC3G as H19 target, and both are inhibited by sulforaphane in prevention of PDAC progression.

Download Full-text

The emerging role of microRNAs in bone remodeling and its therapeutic implications for osteoporosis

Bioscience Reports ◽

10.1042/bsr20180453 ◽

2018 ◽

Vol 38 (3) ◽

Cited By ~ 33

Author(s):

Qianyun Feng ◽

Sheng Zheng ◽

Jia Zheng

Keyword(s):

Bone Remodeling ◽

Noncoding Rna ◽

Target Genes ◽

Epigenetic Modification ◽

Therapeutic Implications ◽

Small Noncoding Rna ◽

Genetic And Environmental Factors ◽

Underlying Mechanisms ◽

Post Transcriptional Regulation

Osteoporosis, a common and multifactorial disease, is influenced by genetic factors and environments. However, the pathogenesis of osteoporosis has not been fully elucidated yet. Recently, emerging evidence suggests that epigenetic modifications may be the underlying mechanisms that link genetic and environmental factors with increased risks of osteoporosis and bone fracture. MicroRNA (miRNA), a major category of small noncoding RNA with 20–22 bases in length, is recognized as one important epigenetic modification. It can mediate post-transcriptional regulation of target genes with cell differentiation and apoptosis. In this review, we aimed to profile the role of miRNA in bone remodeling and its therapeutic implications for osteoporosis. A deeper insight into the role of miRNA in bone remodeling and osteoporosis can provide unique opportunities to develop a novel diagnostic and therapeutic approach of osteoporosis.

Download Full-text

Roles of MicroRNA-34a in Epithelial to Mesenchymal Transition, Competing Endogenous RNA Sponging and Its Therapeutic Potential

International Journal of Molecular Sciences ◽

10.3390/ijms20040861 ◽

2019 ◽

Vol 20 (4) ◽

pp. 861 ◽

Cited By ~ 9

Author(s):

Dongsong Nie ◽

Jiewen Fu ◽

Hanchun Chen ◽

Jingliang Cheng ◽

Junjiang Fu

Keyword(s):

Cancer Therapy ◽

Cancer Progression ◽

Noncoding Rna ◽

Epithelial To Mesenchymal Transition ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Circular Rna ◽

Signal Pathways ◽

Competing Endogenous Rna ◽

Mesenchymal Transition

MicroRNA-34a (miR-34a), a tumor suppressor, has been reported to be dysregulated in various human cancers. MiR-34a is involves in certain epithelial-mesenchymal transition (EMT)-associated signal pathways to repress tumorigenesis, cancer progression, and metastasis. Due to the particularity of miR-34 family in tumor-associated EMT, the significance of miR-34a is being increasingly recognized. Competing endogenous RNA (ceRNA) is a novel concept involving mRNA, circular RNA, pseudogene transcript, and long noncoding RNA regulating each other’s expressions using microRNA response elements to compete for the binding of microRNAs. Studies showed that miR-34a is efficient for cancer therapy. Here, we provide an overview of the function of miR-34a in tumor-associated EMT. ceRNA hypothesis plays an important role in miR-34a regulation in EMT, cancer progression, and metastasis. Its potential roles and challenges as a microRNA therapeutic candidate are discussed. As the negative effect on cancer progression, miR-34a should play crucial roles in clinical diagnosis and cancer therapy.

Download Full-text

MicroRNAs in endometriosis: biological function and emerging biomarker candidates†

Biology of Reproduction ◽

10.1093/biolre/ioz014 ◽

2019 ◽

Vol 101 (6) ◽

pp. 1167-1178 ◽

Cited By ~ 6

Author(s):

Sarah Bjorkman ◽

Hugh S Taylor

Keyword(s):

Noncoding Rna ◽

Target Genes ◽

Biological Function ◽

Transcriptional Regulators ◽

Circulating Mirnas ◽

Common Chronic Disease ◽

Rna Molecules ◽

Small Noncoding Rna ◽

Reproductive Aged Women ◽

Delayed Time

AbstractMicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.

Download Full-text

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

BioMed Research International ◽

10.1155/2015/823620 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Jian Wang ◽

Yong Du ◽

Xiaoming Liu ◽

William C. Cho ◽

Yinxue Yang

Keyword(s):

Colon Cancer ◽

Noncoding Rna ◽

Cancer Metastasis ◽

Target Genes ◽

Signaling Networks ◽

Metastatic Colon Cancer ◽

Rna Molecules ◽

Small Noncoding Rna ◽

P53 Signaling ◽

Colon Cancer Metastasis

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

Download Full-text

Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines

BioMed Research International ◽

10.1155/2015/821761 ◽

2015 ◽

Vol 2015 ◽

pp. 1-19 ◽

Cited By ~ 17

Author(s):

Emmanuelle Berger ◽

Nathalie Vega ◽

Michèle Weiss-Gayet ◽

Alain Géloën

Keyword(s):

Hepatocellular Carcinoma ◽

Signaling Pathways ◽

Hepg2 Cell ◽

Cell Lines ◽

Cancer Progression ◽

High Glucose ◽

Gene Network ◽

Target Genes ◽

Human Hepatocellular Carcinoma ◽

Network Analyses

Cancer progression may be affected by metabolism. In this study, we aimed to analyze the effect of glucose on the proliferation and/or survival of human hepatocellular carcinoma (HCC) cells. Human gene datasets regulated by glucose were compared to gene datasets either dysregulated in HCC or regulated by other signaling pathways. Significant numbers of common genes suggested putative involvement in transcriptional regulations by glucose. Real-time proliferation assays using high (4.5 g/L)versuslow (1 g/L) glucose on two human HCC cell lines and specific inhibitors of selected pathways were used for experimental validations. High glucose promoted HuH7 cell proliferation but not that of HepG2 cell line. Gene network analyses suggest that gene transcription by glucose could be mediated at 92% through ChREBP in HepG2 cells, compared to 40% in either other human cells or rodent healthy liver, with alteration of LKB1 (serine/threonine kinase 11) and NOX (NADPH oxidases) signaling pathways and loss of transcriptional regulation of PPARGC1A (peroxisome-proliferator activated receptors gamma coactivator 1) target genes by high glucose. Both PPARA and PPARGC1A regulate transcription of genes commonly regulated by glycolysis, by the antidiabetic agent metformin and by NOX, suggesting their major interplay in the control of HCC progression.

Download Full-text

Investigation and Identification of let-7a Related Functional Proteins in Gastric Carcinoma by Proteomics

Analytical Cellular Pathology ◽

10.1155/2012/691218 ◽

2012 ◽

Vol 35 (4) ◽

pp. 285-295 ◽

Cited By ~ 5

Author(s):

Yimin Zhu ◽

Xingyuan Xiao ◽

Lairong Dong ◽

Zhiming Liu

Keyword(s):

Gastric Carcinoma ◽

Noncoding Rna ◽

Target Genes ◽

Rho Gtpase ◽

Two Dimensional Gel Electrophoresis ◽

Gastric Carcinoma Cell ◽

Rna Molecules ◽

Small Noncoding Rna

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth bothin vitroandin vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected by high throughout screening. The cell line of SGC-7901 stablely overexpressing let-7a was successfully established by gene cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was applied to analyze 2-DE images. Ten different protein spots were identified by MALDI-TOF-MS, and they may be the proteins associated with let-7a function. The overexpressed proteins included Antioxidant protein 2, Insulin–like growth factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho–GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2 and Fibronectin) were confirmed by western blot analysis. The data suggest that these differential proteins are involved in a novel let-7a signal pathway and these findings provide the basis to investigate the functional mechanisms of let-7a in gastric carcinoma.

Download Full-text

Suppression of Tumor Growth, Metastasis, and Signaling Pathways by Reducing FOXM1 Activity in Triple Negative Breast Cancer

Cancers ◽

10.3390/cancers12092677 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2677

Author(s):

Parama Dey ◽

Alexander Wang ◽

Yvonne Ziegler ◽

Sung Hoon Kim ◽

Dorraya El-Ashry ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Signaling Pathways ◽

Triple Negative Breast Cancer ◽

Target Genes ◽

Triple Negative ◽

Therapeutic Potential ◽

Breast Cancer Subtype ◽

Cell Renewal ◽

Mesenchymal Transition

Metastasis-related complications account for the overwhelming majority of breast cancer mortalities. Triple negative breast cancer (TNBC), the most aggressive breast cancer subtype, has a high propensity to metastasize to distant organs, leading to poor patient survival. The forkhead transcription factor, FOXM1, is especially upregulated and overexpressed in TNBC and is known to regulate multiple signaling pathways that control many key cancer properties, including proliferation, invasiveness, stem cell renewal, and therapy resistance, making FOXM1 a critical therapeutic target for TNBC. In this study, we test the effectiveness of a novel class of 1,1-diarylethylene FOXM1 inhibitory compounds in suppressing TNBC cell migration, invasion, and metastasis using in vitro cell culture and in vivo tumor models. We show that these compounds inhibit the motility and invasiveness of TNBC MDA-MB-231 and DT28 cells, along with reducing the expression of important epithelial to mesenchymal transition (EMT) associated genes. Further, orthotopic tumor studies in NOD-SCID-gamma (NSG) mice demonstrate that these compounds reduce FOXM1 expression and suppress TNBC tumor growth as well as distant metastasis. Gene expression and protein analyses confirm the decreased levels of EMT factors and FOXM1-regulated target genes in tumors and metastatic lesions in the inhibitor-treated animals. The findings suggest that these FOXM1 suppressive compounds may have therapeutic potential in treating triple negative breast cancer, with the aim of reducing tumor progression and metastatic outgrowth.

Download Full-text

MicroRNAs and angiogenesis: a new era for the management of colorectal cancer

Cancer Cell International ◽

10.1186/s12935-021-01920-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yufei Tang ◽

Shaoqi Zong ◽

Hailun Zeng ◽

Xiaofeng Ruan ◽

Liting Yao ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Noncoding Rna ◽

Target Genes ◽

Tumour Progression ◽

Cell Cycle Checkpoint ◽

Tumour Angiogenesis ◽

Small Noncoding Rna ◽

Wide Range ◽

Migration Pathways

AbstractMicroRNAs (miRNAs) are a class of small noncoding RNA molecules containing only 20–22 nucleotides. MiRNAs play a role in gene silencing and translation suppression by targeting and binding to mRNA. Proper control of miRNA expression is very important for maintaining a normal physiological environment because miRNAs can affect most cellular pathways, including cell cycle checkpoint, cell proliferation, and apoptosis pathways, and have a wide range of target genes. With these properties, miRNAs can modulate multiple signalling pathways involved in cancer development, such as cell proliferation, apoptosis, and migration pathways. MiRNAs that activate or inhibit the molecular pathway related to tumour angiogenesis are common topics of research. Angiogenesis promotes tumorigenesis and metastasis by providing oxygen and diffusible nutrients and releasing proangiogenic factors and is one of the hallmarks of tumour progression. CRC is one of the most common tumours, and metastasis has always been a difficult issue in its treatment. Although comprehensive treatments, such as surgery, radiotherapy, chemotherapy, and targeted therapy, have prolonged the survival of CRC patients, the overall response is not optimistic. Therefore, there is an urgent need to find new therapeutic targets to improve CRC treatment. In a series of recent reports, miRNAs have been shown to bidirectionally regulate angiogenesis in colorectal cancer. Many miRNAs can directly act on VEGF or inhibit angiogenesis through other pathways (HIF-1a, PI3K/AKT, etc.), while some miRNAs, specifically many exosomal miRNAs, are capable of promoting CRC angiogenesis. Understanding the mechanism of action of miRNAs in angiogenesis is of great significance for finding new targets for the treatment of tumour angiogenesis. Deciphering the exact role of specific miRNAs in angiogenesis is a challenge due to the high complexity of their actions. Here, we describe the latest advances in the understanding of miRNAs and their corresponding targets that play a role in CRC angiogenesis and discuss possible miRNA-based therapeutic strategies.

Download Full-text

Molecular Mechanisms of Colon Cancer Progression and Metastasis: Recent Insights and Advancements

International Journal of Molecular Sciences ◽

10.3390/ijms22010130 ◽

2020 ◽

Vol 22 (1) ◽

pp. 130

Author(s):

Ahmed Malki ◽

Rasha Abu ElRuz ◽

Ishita Gupta ◽

Asma Allouch ◽

Semir Vranic ◽

...

Keyword(s):

Signaling Pathways ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Target Genes ◽

Cellular Signaling ◽

Clinical Care ◽

Underlying Mechanism ◽

Cellular Mechanisms ◽

Colon Cancer Progression ◽

Crc Management

Colorectal cancer (CRC), the third most common type of cancer, is the second leading cause of cancer-related mortality rates worldwide. Although modern research was able to shed light on the pathogenesis of CRC and provide enhanced screening strategies, the prevalence of CRC is still on the rise. Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, analyzing signaling pathways involved in CRC metastasis is necessary to elucidate the underlying mechanism of CRC progression and pharmacotherapy. This review focused on target genes as well as various cellular signaling pathways including Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF, and JAKs/STAT3, which are associated with CRC progression and metastasis. Additionally, alternations in methylation patterns in relation with signaling pathways involved in regulating various cellular mechanisms such as cell cycle, transcription, apoptosis, and angiogenesis as well as invasion and metastasis were also reviewed. To date, understanding the genomic and epigenomic instability has identified candidate biomarkers that are validated for routine clinical use in CRC management. Nevertheless, better understanding of the onset and progression of CRC can aid in the development of early detection molecular markers and risk stratification methods to improve the clinical care of CRC patients.

Download Full-text