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1.
Prognostic utility and clinical significance of lysyl oxidase-like 2 protein expression in digestive system cancers.
Zhang, Y, Liu, W, Xu, J
Journal of cellular physiology. 2019;(11):20713-20720
Abstract
Lysyl oxidase-like 2 (LOXL2) participates in the occurrence and development of digestive system cancers (DSCs). The aim of this study was to determine whether LOXL2 protein could serve as a prognostic biomarker in patients with DSCs. Relevant studies published before October 1, 2018 were identified from a comprehensive literature review in PubMed, Web of Science, and Embase. This meta-analysis was conducted via STATA/SE 14.1 software. Finally, a total of 12 publications and 6 different kinds of DSCs were identified. Meta-analysis indicated that increased expression of LOXL2 protein was significantly correlated with reduced overall survival (hazard ratios [HR]: 1.52; 95% confidence interval [CI]: 1.32-1.72) and worse progression-free survival/disease-free survival (HR: 2.15; 95% CI: 1.48-2.83) in cases with DSCs. In addition, clinicopathological parameters, including tumor invasion, lymph node metastasis, distant metastasis, and clinical stage were significantly related to LOXL2 protein expression in DSCs. High LOXL2 protein expression is significantly associated with worse clinical outcomes in DSCs and its expression level may represent a candidate prognostic biomarker in these cancers.
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2.
Long non-coding RNAs in retinoblastoma.
Yang, M, Wei, W
Pathology, research and practice. 2019;(8):152435
Abstract
Retinoblastoma represents 3% of all childhood cancers and is the most common intraocular malignant tumor with a highly aggressive and metastatic phenotype. While recent genetic and epigenetic studies have reported new insights into the mechanism of retinoblastoma development, the involvement of regulatory non-coding RNAs remains unclear. Long non-coding RNAs (lncRNAs) are a group of endogenous non-protein-coding RNAs with the capacity to regulate gene expression at multiple levels. Recent evidence has shown that lncRNAs can regulate many cellular processes, such as cell proliferation, differentiation, migration, and invasion. Several lncRNAs, including BANCR, AFAP1-AS1, NEAT1, XIST, ANRIL, PlncRNA-1, HOTAIR, PANDAR, DANCR, and THOR, promote the progression and metastasis of retinoblastoma. However, some lncRNAs, such as MEG3, MT1JP, and H19, play a tumor suppressive role. Our review summarizes the functional role of lncRNAs in retinoblastoma and their potential clinical applications for diagnosis, prognosis, and treatment.
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3.
ZFAS1: A novel vital oncogenic lncRNA in multiple human cancers.
He, A, He, S, Li, X, Zhou, L
Cell proliferation. 2019;(1):e12513
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Abstract
Long noncoding RNAs (lncRNAs) are a class of noncoding, endogenous, single-stranded RNAs longer than 200 nucleotides in length that are transcribed by RNA polymerase II. Mounting evidence has indicated that lncRNAs play key roles in several physiological and pathological processes by modifying gene expression at the transcriptional, posttranscriptional, epigenetic, and translation levels. Many reports have demonstrated that lncRNAs function as potential oncogene or tumour suppressors and thus play vital regulatory roles in tumourigenesis and tumour progression. ZNFX1 antisense RNA 1 (ZFAS1), a novel lncRNA transcribed in the antisense orientation of zinc finger NFX1-type containing 1(ZNFX1), was found to be increased in multiple cancers, such as gastric cancer and hepatocellular carcinoma, contributing to cancer development and progression. In the present review, we summarized recent progression on study of the functions and underlying molecular mechanisms of ZFAS1 related to occurrence and development of multiple cancers.
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4.
Long non-coding RNAs are emerging targets of phytochemicals for cancer and other chronic diseases.
Mishra, S, Verma, SS, Rai, V, Awasthee, N, Chava, S, Hui, KM, Kumar, AP, Challagundla, KB, Sethi, G, Gupta, SC
Cellular and molecular life sciences : CMLS. 2019;(10):1947-1966
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Abstract
The long non-coding RNAs (lncRNAs) are the crucial regulators of human chronic diseases. Therefore, approaches such as antisense oligonucleotides, RNAi technology, and small molecule inhibitors have been used for the therapeutic targeting of lncRNAs. During the last decade, phytochemicals and nutraceuticals have been explored for their potential against lncRNAs. The common lncRNAs known to be modulated by phytochemicals include ROR, PVT1, HOTAIR, MALAT1, H19, MEG3, PCAT29, PANDAR, NEAT1, and GAS5. The phytochemicals such as curcumin, resveratrol, sulforaphane, berberine, EGCG, and gambogic acid have been examined against lncRNAs. In some cases, formulation of phytochemicals has also been used. The disease models where phytochemicals have been demonstrated to modulate lncRNAs expression include cancer, rheumatoid arthritis, osteoarthritis, and nonalcoholic fatty liver disease. The regulation of lncRNAs by phytochemicals can affect multi-steps of tumor development. When administered in combination with the conventional drugs, phytochemicals can also produce synergistic effects on lncRNAs leading to the sensitization of cancer cells. Phytochemicals target lncRNAs either directly or indirectly by affecting a wide variety of upstream molecules. However, the potential of phytochemicals against lncRNAs has been demonstrated mostly by preclinical studies in cancer models. How the modulation of lncRNAs by phytochemicals produce therapeutic effects on cancer and other chronic diseases is discussed in this review.
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5.
Modulatory effects of curcumin on heat shock proteins in cancer: A promising therapeutic approach.
Forouzanfar, F, Barreto, G, Majeed, M, Sahebkar, A
BioFactors (Oxford, England). 2019;(5):631-640
Abstract
Cancer metastasis represents a multistep process, including alteration of cell adhesion/motility in the microenvironment and sustained angiogenesis, which is essential for supporting cancer growth in tissues that are distant from the primary tumor. There is growing evidence suggesting that heat shock proteins (HSPs) (also known as heat stress proteins), which constitute a family of stress-inducible proteins, may be involved in the pathogenesis of cancer. Curcumin (diferuloylmethane) is a potent anti-inflammatory, antioxidant, antimicrobial, and antitumor agent. Curcumin has been shown to regulate different members of HSPs including HSP27, HSP40, HSP60, HSP70, and HSP90 in cancer. Here, we present extent findings suggesting that curcumin may act as a potential therapeutic agent for the treatment of cancer through its regulation of HSPs.
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Triterpene Acid (3-O-p-Coumaroyltormentic Acid) Isolated From Aronia Extracts Inhibits Breast Cancer Stem Cell Formation through Downregulation of c-Myc Protein.
Choi, HS, Kim, SL, Kim, JH, Deng, HY, Yun, BS, Lee, DS
International journal of molecular sciences. 2018;(9)
Abstract
Cancer stem cells (CSCs) are drug-resistant and radiation-resistant cancer cells that are responsible for tumor progression and maintenance, cancer recurrence, and metastasis. Targeting breast CSCs with phytochemicals is a new paradigm for cancer prevention and treatment. In this study, activity-guided fractionation from mammosphere formation inhibition assays, repeated chromatographic preparations over silica gel, preparatory thin layer chromatography, and HPLC using aronia extracts led to the isolation of one compound. Using ¹H and 13C 2-dimensional nuclear magnetic resonance (NMR) as well as electrospray ionization (ESI) mass spectrometry, the isolated compound was identified as 3-O-p-coumaroyltormentic acid. This compound inhibits breast cancer cell proliferation and mammosphere formation in a dose-dependent manner and reduces the CD44high/CD24low subpopulation and aldehyde dehydrogenase (ALDH)-expressing cell population as well as the expression of the self-renewal-related genes CD44, SOX2, and OCT4.3-O-p-Coumaroyltormentic acid preferentially reduced the protein levels of c-Myc, which is a CSC survival factor, by inducing c-Myc degradation. These findings indicate the novel utilization of 3-O-p-coumaroyltormentic acid for breast cancer therapy via disruption of c-Myc protein, which is a CSC survival factor.
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7.
Role of lncRNAs in the cancer development and progression and their regulation by various phytochemicals.
Rathinasamy, B, Velmurugan, BK
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;:242-248
Abstract
Long non coding RNAs (lncRNAs) are involved in modulating the expression of other non-coding RNAs (ncRNA), such as microRNAs, or target proteins through the epigenetic, transcriptional, or post-transcriptional regulations. Genomic mutations in cancer reside inside regions that do not code for proteins and these regions are often transcribed into long non coding RNAs (lncRNAs). Emerging evidences have revealed an intense involvement of lncRNAs in the cancer development and progression. Recently, emerging evidences have depicted that the phytochemicals interact with lncRNAs to modulate their activities. Such findings are highly important for the identification of therapeutic strategies against diseases that are particularly associated with an aberrant lncRNA signaling. This review aims at deciphering the role of lncRNAs in the cancer development and progression, and their regulation by various phytochemicals.
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8.
Human Thymidylate Synthase Inhibitors Halting Ovarian Cancer Growth.
Ferrari, S, Severi, L, Pozzi, C, Quotadamo, A, Ponterini, G, Losi, L, Marverti, G, Costi, MP
Vitamins and hormones. 2018;:473-513
Abstract
Human thymidylate synthase (hTS) has an important role in DNA biosynthesis, thus it is essential for cell survival. TS is involved in the folate pathways, specifically in the de novo pyrimidine biosynthesis. Structure and functions are intimately correlated, account for cellular activity and, in a broader view, with in vivo mechanisms. hTS is a target for anticancer agents, some of which are clinical drugs. The understanding of the detailed mechanism of TS inhibition by currently used drugs and of the interaction with the mechanism of action of other anticancer agents can suggest new perspective of TS inhibition able to improve the anticancer effect and to overcome drug resistance. TS-targeting drugs in therapy today are inhibitors that bind at the active site and that mostly resemble the substrates. Nonsubstrate analogs offer an opportunity for allosteric binding and novel mode of inhibition in the cancer cells. This chapter illustrates the relationship among the large number of hTS actions at molecular and clinical levels, its role as a target for ovarian cancer therapy, in particular in cases of overexpression of hTS and other folate proteins such as those induced by platinum drug treatments, and address the potential combination of TS inhibitors with other suitable anticancer agents.
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9.
The role of long non-coding RNA AFAP1-AS1 in human malignant tumors.
Ji, D, Zhong, X, Jiang, X, Leng, K, Xu, Y, Li, Z, Huang, L, Li, J, Cui, Y
Pathology, research and practice. 2018;(10):1524-1531
Abstract
OBJECTIVES Long non-coding RNAs (lncRNAs) are a type Table of endogenous RNA longer than 200 nucleotides in length, and this kind of RNAs lack or possess limited ability of coding proteins. A large number of studies have demonstrated that lncRNAs could take part in massive biological processes, such as transcriptional activation and interference, cellular differentiation, proliferation, migration, invasion and apoptosis. The abnormal expression of lncRNAs has been clarified to play extremely important roles in various diseases, especially in human cancers. LncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is a newly recognized cancer-related lncRNA deriving from the antisense strand of DNA at the AFAP1 coding gene locus. A slew of new studies suggest that AFAP1-AS1 is involved in many kinds of malignant tumors. Moreover, in recent years, the dysregulated expression of AFAP1-AS1 has been confirmed to be associated with oncogenesis and tumor progression. Evidence has increasingly shown that AFAP1-AS1 could probably serve as a novel potential molecular biomarker in tumor diagnosis and therapeutic target in tumor treatment. In this review, we sum up present stage new hottest research issues in respect of the biological functions and molecular mechanisms of AFAP1-AS1 in occurrence and progression of human tumors. MATERIALS AND METHODS In this review, we summarize the recent researches about the expression and molecular biological mechanisms of lncRNA AFAP1-AS1 in tumor development. Existing relevant studies are acquired and analyzed by searching Pubmed, BioMedNet, GEO database and Academic Search Elit systematically. RESULTS Long non-coding RNA AFAP1-AS1 is an important tumor-associated lncRNA and its aberrant expression has been found in many malignancies so far, including pancreatic ductal adenocarcinoma, cholangiocarcinoma, gallbladder cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, esophageal cancer, nasopharyngeal carcinoma, lung cancer, ovarian cancer, breast cancer, retinoblastoma, laryngeal cancer, tongue squamous cell carcinoma and thyroid cancer. In addition, the dysregulated expression of AFAP1-AS1 is related to carcinogensis, overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and tumor progression containing lymph node metastasis, distant metastasis, histological grade, tumor size and tumor stage. CONCLUSIONS A series of studies provide detailed information to understand lncRNA AFAP1-AS1 role in various human cancers. LncRNA AFAP1-AS1 is an oncogene in tumors that have been studied so far, and it may act as a useful tumor biomarker and therapeutic target.
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10.
AIP and the somatostatin system in pituitary tumours.
Ibáñez-Costa, A, Korbonits, M
The Journal of endocrinology. 2017;(3):R101-R116
Abstract
Classic somatostatin analogues aimed at somatostatin receptor type 2, such as octreotide and lanreotide, represent the mainstay of medical treatment for acromegaly. These agents have the potential to decrease hormone secretion and reduce tumour size. Patients with a germline mutation in the aryl hydrocarbon receptor-interacting protein gene, AIP, develop young-onset acromegaly, poorly responsive to pharmacological therapy. In this review, we summarise the most recent studies on AIP-related pituitary adenomas, paying special attention to the causes of somatostatin resistance; the somatostatin receptor profile including type 2, type 5 and truncated variants; the role of G proteins in this pathology; the use of first and second generation somatostatin analogues; and the role of ZAC1, a zinc-finger protein with expression linked to AIP in somatotrophinoma models and acting as a key mediator of octreotide response.