Expression, Regulation, and Role of an Oligopeptide Transporter: PEPT1 in Tumors

: PEPT1 is a vital member of the proton-dependent oligopeptide transporters family (POTs). Many studies have confirmed that PEPT1 plays a critical role in the absorption of dipeptides, tripeptides, and pseudopeptides in the intestinal tract. In recent years, several studies have found that PEPT1 is highly expressed in malignant tumor tissues and cells. The abnormal expression of PEPT1 in tumors may be closely related to the progress of tumors, and hence, could be considered as a potential molecular biomarker for the diagnosis, treatment, and prognosis in malignant tumors. Furthermore, PEPT1 can be used as the delivery target to mediate the targeted delivery of antitumor drugs. Herein, the expression, regulation, and role of PEPT1 in tumors in recent years were reviewed.

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KLF2 Inhibits the Migration and Invasion of Prostate Cancer Cells by Downregulating MMP2

American Journal of Men s Health ◽

10.1177/1557988318816907 ◽

2018 ◽

Vol 13 (1) ◽

pp. 155798831881690 ◽

Cited By ~ 5

Author(s):

Binshuai Wang ◽

Mingyuan Liu ◽

Yimeng Song ◽

Changying Li ◽

Shudong Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Suppressor ◽

Cell Function ◽

Malignant Tumors ◽

Suppressor Gene ◽

Migration And Invasion ◽

Tissue Samples ◽

Tumor Tissues ◽

Luciferase Activity Assay

KLF2, a member of the Kruppel-like factor (KLF) family, is thought to be a tumor suppressor in many kinds of malignant tumors. Its functions in prostate cancer (PCa) are unknown. This study aimed to explore the role of KLF2 in the migration and invasion of PCa cells. The expression of KLF2 was measured by immunohistochemistry in PCa tissues and in paired non-tumor tissues. KLF2 and MMP2 expression in cells was measured by Western blot and RT-qPCR. Adenoviruses and siRNAs were used in cell function tests to investigate the role of KLF2 in regulating MMP2. Interactions between KLF2 and MMP2 were analyzed by a luciferase activity assay. The present study, for the first time, identified that KLF2 was downregulated both in PCa clinical tissue samples and in cancer cell lines. The overexpression of KLF2 inhibited the migration and invasion of PCa cells via the suppression of MMP2.This study demonstrates that KLF2 might act as a tumor suppressor gene in PCa and that the pharmaceutical upregulation of KLF2 may be a potential approach for treatment.

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Role of miRNAs In Cancer Diagnostics And Therapy: A Recent Update

Current Pharmaceutical Design ◽

10.2174/1381612827666211109113305 ◽

2021 ◽

Vol 27 ◽

Author(s):

Adil A. Sayyed ◽

Piyush Gondaliya ◽

Palak Bhat ◽

Mukund Mali ◽

Neha Arya ◽

...

Keyword(s):

Targeted Delivery ◽

Tumor Invasion ◽

Cancer Metastasis ◽

Critical Role ◽

Delivery Systems ◽

Cancer Diagnostics ◽

Disease Monitoring ◽

The Stability ◽

Diagnostics And Therapy

: The discovery of miRNAs has been one of the revolutionary developments and has led to the advent of new diagnostic and therapeutic opportunities for the management of cancer. In this regard, miRNA dysregulation has been shown to play a critical role in various stages of tumorigenesis, including tumor invasion, metastasis as well as angiogenesis. Therefore, miRNA profiling can provide accurate fingerprints for the development of diagnostic and therapeutic platforms. This review discusses the recent discoveries of miRNA-based tools for early detection of cancer as well as disease monitoring in cancers that are common, like breast, lung, hepatic, colorectal, oral and brain cancer. Based on the involvement of miRNA in different cancers as oncogenic miRNA or tumor suppressor miRNA, the treatment with miRNA inhibitors or mimics is recommended. However, the stability and targeted delivery of miRNA remain the major limitations of miRNA delivery. In relation to this, several nanoparticle-based delivery systems have been reported which have effectively delivered the miRNA mimics or inhibitors and showed the potential for transforming these advanced delivery systems from bench to bedside in the treatment of cancer metastasis and chemoresistance. Based on this, we attempted to uncover recently reported advanced nanotherapeutic approaches to deliver the miRNAs in the management of different cancers.

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DUSP12 regulates the tumorigenesis and prognosis of hepatocellular carcinoma

PeerJ ◽

10.7717/peerj.11929 ◽

2021 ◽

Vol 9 ◽

pp. e11929

Author(s):

Gaoda Ju ◽

Tianhao Zhou ◽

Rui Zhang ◽

Xiaozao Pan ◽

Bing Xue ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Immune Cells ◽

Malignant Tumors ◽

Critical Role ◽

Normal Liver ◽

Functional Enrichment ◽

Loss Of Function ◽

Liver Tissues

Background Dual specificity protein phosphatase (DUSP)12 is an atypical member of the protein tyrosine phosphatase family, which are overexpressed in multiple types of malignant tumors. This protein family protect cells from apoptosis and promotes the proliferation and motility of cells. However, the pathological role of DUSP12 in hepatocellular carcinoma (HCC) is incompletely understood. Methods We analyzed mRNA expression of DUSP12 between HCC and normal liver tissues using multiple online databases, and explored the status of DUSP12 mutants using the cBioPortal database. The correlation between DUSP12 expression and tumor-infiltrating immune cells was demonstrated using the Tumor Immune Estimation Resource database and the Tumor and Immune System Interaction Database. Loss of function assay was utilized to evaluate the role of DUSP12 in HCC progression. Results DUSP12 had higher expression along with mRNA amplification in HCC tissues compared with those in normal liver tissues, which suggested that higher DUSP12 expression predicted shorter overall survival. Analyses of functional enrichment of differentially expressed genes suggested that DUSP12 regulated HCC tumorigenesis, and that knockdown of DUSP12 expression by short hairpin (sh)RNA decreased the proliferation and migration of HCC cells. Besides, DUSP12 expression was positively associated with the infiltration of cluster of differentiation (CD)4+ T cells (especially CD4+ regulatory T cells), macrophages, neutrophils and dendritic cells. DUSP12 expression was positively associated with immune-checkpoint moieties, and was downregulated in a C3 immune-subgroup of HCC (which had the longest survival). Conclusion These data suggest that DUSP12 may have a critical role in the tumorigenesis, infiltration of immune cells, and prognosis of HCC.

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Creatine Kinase-BB Activity in Malignant Tumors and in Sera from Patients with Malignant Diseases

Tumori Journal ◽

10.1177/030089168907500604 ◽

1989 ◽

Vol 75 (6) ◽

pp. 537-541 ◽

Cited By ~ 3

Author(s):

Ante Roguljić ◽

Tayfour Safwan ◽

Viktor Šeparović

Keyword(s):

Creatine Kinase ◽

Enzyme Activity ◽

Parotid Gland ◽

Malignant Tumor ◽

Malignant Tumors ◽

Average Rate ◽

Malignant Diseases ◽

Creatine Kinase Bb ◽

Serum Activity ◽

Tumor Tissues

Creatine kinase (CK EC 2.7.3.2) and CK-BB activity was analyzed in 41 malignant tumors of 6 different sites and different histological structures. The same analyses were done on 150 sera of patients with malignant diseases of various localizations. The rate of CK activity was determined kinetical-ly, whereas tissue and serum CK-BB were separated chromatographically (Mercer). Insofar as malignant tumor tissues are concerned, the highest average rate of CK-BB activity was detected in tumors of the prostate (mean 1450 IU/g), and the lowest in tumors of the parotid gland (mean 5.2 IU/g). CK-BB was detected by the Mercer technique in 56 (37.3 %) of 150 analyzed sera of patients with malignant diseases. The rate of CK activity in sera of patients with malignant diseases was 8 to 74 IU/I. In comparison with the site of the malignant process no significant CK serum activity differences were observed. T2-T3 tumors did not significantly influence the activity of either CK or CK-BB in the case of either tissues or sera (T1-T3). Enzyme activity was found to be much higher - both in tumoral tissue and in sera - with T4 tumors. The highest rate of CK-BB activity was found in sera of patients with malignant tumors of the stomach (mean 8.1 IU/I), and the lowest in malignant tumors of the rectum (mean 1.8 IU/I).

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Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation

Journal of Oncology ◽

10.1155/2010/201026 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 92

Author(s):

Michael C. Schmid ◽

Judith A. Varner

Keyword(s):

Tumor Microenvironment ◽

Tumor Angiogenesis ◽

Malignant Tumors ◽

Critical Role ◽

Myeloid Cells ◽

Suppressor Cells ◽

Myeloid Cell ◽

Promote Tumor Growth ◽

Bone Marrow Derived Cells

Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. Furthermore, we describe a subset of myeloid cells with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy.

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Prospects of application of inhibitors of PD-1/PD-L1 checkpoints in malignant tumors of the stomach and esophagogastric junction

Medical Council ◽

10.21518/2079-701x-2020-20-15-21 ◽

2020 ◽

pp. 15-21

Author(s):

D. D. Sakaeva ◽

A. A. Melnikova

Keyword(s):

Esophagogastric Junction ◽

Kinase Inhibitors ◽

Malignant Tumors ◽

Checkpoint Inhibitors ◽

Combined Therapy ◽

Therapy Response ◽

Treatment Method ◽

Tumor Tissues ◽

Advanced Stages

Malignant tumors of the stomach and esophagogastric junction in advanced stages progress quite aggressively, and the prospects for treatment of these patients remain unpromising. The use of checkpoint-inhibitors has proven to be an advanced treatment method for various types of cancer around the world. In theRussian Federation, nivolumab has been successfully registered as a monotherapy for common or recurrent stomach or esophagogastric junction cancer after two or more lines of systemic antitumor drug therapy. This literature review focuses on the use of registered checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) as mono- and/or combined therapy in tumors of the stomach and esophagogastric junction, including tumors with high microsat- ellite instability (MSI-high). This review includes a description of the main therapeutic approaches using checkpoint inhibitors: prescription in mono-mode, in combination with other checkpoint inhibitors (ipilimumab) and cytotoxic drugs, and in combination with tyrosine kinase inhibitors (regorafenib). Issues of efficiency and tolerability of these combinations in patients in different therapeutic lines are considered. The role of possible predictors of therapy response is analyzed: biomarkers such as PD-Ll, MSI, dMMR and TMB expression in tumor tissues as well as immunofenotyping in fresh biopsy samples are evaluated. This article reviews and evaluates the strengths and weaknesses of checkpoint inhibitors and their possible uses.

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LncRNA H19 Suppresses Osteosarcomagenesis by Regulating snoRNAs and DNA Repair Protein Complexes

Frontiers in Genetics ◽

10.3389/fgene.2020.611823 ◽

2021 ◽

Vol 11 ◽

Author(s):

An Xu ◽

Mo-Fan Huang ◽

Dandan Zhu ◽

Julian A. Gingold ◽

Danielle A. Bazer ◽

...

Keyword(s):

Tumor Suppressor ◽

Molecular Mechanisms ◽

Malignant Tumors ◽

Protein Complexes ◽

Familial Cancer ◽

Critical Role ◽

Childhood And Adolescence ◽

Cancer Syndrome ◽

Li Fraumeni Syndrome

Osteosarcoma is one of the most frequent common primary malignant tumors in childhood and adolescence. Long non-coding RNAs (lncRNAs) have been reported to regulate the initiation and progression of tumors. However, the exact molecular mechanisms involving lncRNA in osteosarcomagenesis remain largely unknown. Li-Fraumeni syndrome (LFS) is a familial cancer syndrome caused by germline p53 mutation. We investigated the tumor suppressor function of lncRNA H19 in LFS-associated osteosarcoma. Analyzing H19-induced transcriptome alterations in LFS induced pluripotent stem cell (iPSC)-derived osteoblasts, we unexpectedly discovered a large group of snoRNAs whose expression was significantly affected by H19. We identified SNORA7A among the H19-suppressed snoRNAs. SNORA7A restoration impairs H19-mediated osteogenesis and tumor suppression, indicating an oncogenic role of SNORA7A. TCGA analysis indicated that SNORA7A expression is associated with activation of oncogenic signaling and poor survival in cancer patients. Using an optimized streptavidin-binding RNA aptamer designed from H19 lncRNA, we revealed that H19-tethered protein complexes include proteins critical for DNA damage response and repair, confirming H19's tumor suppressor role. In summary, our findings demonstrate a critical role of H19-modulated SNORA7A expression in LFS-associated osteosarcomas.

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Role of HDAC6 and Its Selective Inhibitors in Gastrointestinal Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.719390 ◽

2021 ◽

Vol 9 ◽

Author(s):

Bingyi Zhou ◽

Deliang Liu ◽

Yuyong Tan

Keyword(s):

Cardiovascular Diseases ◽

Gastrointestinal Cancer ◽

Histone Deacetylases ◽

Digestive System ◽

Malignant Tumors ◽

Clinicopathological Characteristics ◽

Cancer Occurrence ◽

Tumor Tissues ◽

Human Digestive System

Worldwide, cancer is the second leading cause of mortality after cardiovascular diseases. Among the numerous malignant tumors in human, digestive system cancers are the primary cause of morbidity and mortality. Acetylation and deacetylation are crucially involved in cancer occurrence and development; in addition, the deacetylation process is regulated by histone deacetylases (HDACs). Among the 18 human HDACs that have been reported, HDAC6 has been widely studied. There is upregulated HDAC6 expression in numerous types of tumor tissues and is closely associated with clinicopathological characteristics. Moreover, several HDAC6 inhibitors have been identified; furthermore, there has been extensive research on their ability to inhibit the growth of many tumors. This review summarizes the roles of HDAC6 in different primary digestive system malignancies.

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Nestin +/CD31 + Cells in the Hypoxic Perivascular Niche Regulate Glioblastoma Chemoresistance by Upregulating JAG1 and DLL4

Neuro-Oncology ◽

10.1093/neuonc/noaa265 ◽

2020 ◽

Author(s):

Zong-Qing Zheng ◽

Jin-Tao Chen ◽

Ming-Cheng Zheng ◽

Li-Juan Yang ◽

Jun-Ming Wang ◽

...

Keyword(s):

Poor Prognosis ◽

Critical Role ◽

High Ratio ◽

Microfluidic Chips ◽

Perivascular Niche ◽

Tumor Tissues ◽

Hes1 Expression ◽

Different Types

Abstract Background Failure of glioblastoma (GBM) therapy is often ascribed to different types of glioblastoma stem-like cells (GSLCs) niche, in particularly, a hypoxic perivascular niche (HPVN) is involved in GBM progression. However, the responsible cells for HPVN remained unclear. Methods Immunostaining was performed to determine the cells that are responsible for HPVN. A hypoxic chamber and 3D microfluidic chips were designed to simulate HPVN based on the pathological features of GBM. The phenotype of GSLCs was evaluated by fluorescence scanning in real-time and proliferation and apoptotic assays. The expression of JAG1, DLL4 and Hes1 was determined by immunostaining, ELISA, western-blotting, and q-PCR. Their clinical progonostic significance in GBM HPVN and total tumor tissues were verified by clinical data and TCGA databases. Results Nestin +/CD31 + cells and pericytes constitute the major part of microvessels in HPVN and high ratio of nestin +/CD31 + cells rather than pericytes were responsible for poor prognosis of GBM. A more real HPVN was simulated by hypoxic coculture system in vitro, which was assembled by 3D microfluidic chips and hypoxic chamber. Nestin +/CD31 + cells in HPVN were derived from GSLCs transdifferentiation and could promote GSLCs chemoresistance by providing more JAG1 and DLL4 to induce down-stream Hes1 overexpression. Poor prognosis of GBM was correlated to Hes1 expression of tumor cells in GBM HPVN, and not correlated with total Hes1 expression in GBM tissues. Conclusion These results hightlighted the critical role of nestin +/CD31 + cells in HPVN that acts in GBM chemoresistance and revealed the distinctive prognostic value of these molecular markers in HPVN.

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The oncoprotein HBXIP – its functions and roles in oncogenesis

Progress in Health Sciences ◽

10.5604/01.3001.0012.8350 ◽

2018 ◽

Vol 8 (2) ◽

pp. 215-222

Author(s):

M. Grudzinska ◽

K. Lomperta ◽

K. Jakubowska ◽

P. Samocik ◽

K. Jarząbek ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Treatment Effectiveness ◽

Malignant Tumors ◽

Interacting Protein ◽

Complement Dependent Cytotoxicity ◽

Tumor Tissues ◽

A Cell ◽

Cancerous Cells

Nowadays, Hepatitis B X interacting protein (HBXIP) is an object of scientists’ interest worldwide. It is a protein with significant involvement in the development of malignant tumors like breast or ovarian cancer. One of the most important functions of HBXIP is the regulation of cell proliferation, which is related to the progression of a cell cycle. Many studies provide the growing number of evidence that HBXIP plays various important roles, including the regulation of a cell cycle through complexes with survivin, belonging to the inhibitors of apoptosis and interactions with transcriptional factors like STAT4, SP1, TFIID or E2F1. It also has the influence on the promotion of tumor angiogenesis thanks to the association with VEGF and FGF8. Another important role of HBXIP is a reprogramming of glucose metabolism to conditions favorable to growing cancerous cells due to regulating the activation of SCO2 and PDHA1. Furthermore, it impacts on the complement-dependent cytotoxicity, also, HBXIP affects on lipid metabolism through disturbing of metabolic pathways of FAS. According to recent studies, HBXIP can be used as a prognostic biomarker in many tumors, including cervical cancer, ovarian cancer, and esophageal squamous cell carcinoma thanks to the high expression of this protein noted exclusively in these tumor tissues. What is even more interesting, it significantly correlates with clinical attributes like metastasis to lymph nodes or grading and in some cases can potentially be used as the indicator of prognosis of treatment effectiveness. The paper is review through main functions of HBXIP and its possible applications.

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