Spectrum of microRNAs and their target genes in cancer: intervention in diagnosis and therapy

Abstract Background: Pancreatic carcinoma (PC) is a severe disease associated with high mortality. Although strategies for cancer therapy made great progress, outcomes of pancreatic ductal adenocarcinoma patients remain extremely poor. Therefore, it is urgent to find novel biomarkers and therapeutic targets to improve outcomes of patients. Methods: To identify general applicable targets for early diagnosis and therapy, we selected related microarray data which including three mRNA microarray datasets GSE62165, GSE15471, GSE32676 and two miRNA datasets GSE24279, GSE32678, and combinative analysis was performed by GEO2R. Functional and pathway enrichment analysis were performed using the DAVID database. MiRTarBase, miRWalk, Diana Tools and TBtools were used to get keys. TCGA database, HPA database and western blot experiments were used to verify diagnostic and prognostic value of key genes.Results: By integrating mRNA and miRNA expression profiles, we identified 114 differentially expressed genes (DEGs) and 114 differentially expressed miRNAs (DEMs), respectively. Furthermore, three overlapping key genes, RUNX2, LAMC2 and FBXO32, were found by compared with DEMs target genes and DEGs. In detail, deregulation of 8 key miRNAs were closely related to poor outcomes and participated in crucial genes regulation which may contribute to build a miRNA biomarker panel for prognosis. Moreover, we confirmed that RUNX2 showed a potential property for distinguishing PC and normal people. We also demonstrated that aberrant over-expression of LAMC2 was associated with poor prognosis of PC patients as well as human tumor status and subtypes. The protein levels of RUNX2 and LAMC2 in PC patients were further verified by IHC from Human Protein Atlas and western blot experiments. Conclusions: In summary, our current study identified that RUNX2 and LAMC2 may be promising targets for early diagnosis and therapy of PC patients.

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Nuclear receptors in disease: the oestrogen receptors

Essays in Biochemistry ◽

10.1042/bse0400157 ◽

2004 ◽

Vol 40 ◽

pp. 157-167 ◽

Cited By ~ 18

Author(s):

Maria Nilsson ◽

Karin Dahlman-Wright ◽

Jan-Åke Gustafsson

Keyword(s):

Nuclear Receptors ◽

Target Genes ◽

Receptor Subtype ◽

Target Tissue ◽

Oestrogen Receptors ◽

Nucleotide Polymorphisms ◽

Cell Type ◽

Single Nucleotide ◽

Beneficial Effects ◽

The Family

For several decades, it has been known that oestrogens are essential for human health. The discovery that there are two oestrogen receptors (ERs), ERalpha and ERbeta, has facilitated our understanding of how the hormone exerts its physiological effects. The ERs belong to the family of ligand-activated nuclear receptors, which act by modulating the expression of target genes. Studies of ER-knockout (ERKO) mice have been instrumental in defining the relevance of a given receptor subtype in a certain tissue. Phenotypes displayed by ERKO mice suggest diseases in which dysfunctional ERs might be involved in aetiology and pathology. Association between single-nucleotide polymorphisms (SNPs) in ER genes and disease have been demonstrated in several cases. Selective ER modulators (SERMs), which are selective with regard to their effects in a certain cell type, already exist. Since oestrogen has effects in many tissues, the goal with a SERM is to provide beneficial effects in one target tissue while avoiding side effects in others. Refined SERMs will, in the future, provide improved therapeutic strategies for existing and novel indications.

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381: Promoter Hypermethylation Profile of Kidney Cancer with New Pro-Apoptotic P53 Target Genes and Possible Clinical Implications

The Journal of Urology ◽

10.1016/s0022-5347(18)32637-5 ◽

2006 ◽

Vol 175 (4S) ◽

pp. 125-125

Author(s):

Frank Christoph ◽

Steffen Weikert ◽

Carsten Kempkensteffen ◽

Martin Schostak ◽

Hans Krause ◽

...

Keyword(s):

Kidney Cancer ◽

Target Genes ◽

Promoter Hypermethylation ◽

Clinical Implications ◽

P53 Target Genes

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RNA in Diagnosis and Therapy

Internal Medicine News ◽

10.1016/s1097-8690(08)70638-3 ◽

2008 ◽

Vol 41 (11) ◽

pp. 34-35

Author(s):

MICHAEL F. MURRAY

Keyword(s):

Diagnosis And Therapy

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Diagnosis and therapy of brain abscesses

Therapeutische Umschau ◽

10.1024/0040-5930.56.11.659 ◽

1999 ◽

Vol 56 (11) ◽

pp. 659-663 ◽

Cited By ~ 4

Author(s):

Nau ◽

Behnke-Mursch

Keyword(s):

Operative Verfahren ◽

Diagnosis And Therapy ◽

Brain Abscesses

Die verursachenden Erreger von Hirnabszessen variieren in Abhängigkeit von der Grunderkrankung. Typisch sind Mischinfektionen aus Aerobiern und Anaerobiern. Hirnabszesse entwickeln sich meist subakut. Sensibelster Entzündungsparameter im Blut ist das C-reaktive Protein (bei 80–90% der Patien-ten erhöht). Die entscheidende diagnostische Maßnahme ist das kraniale CT ohne und mit Kontrastmittel (KM). Die rasche Kultur von Abszeßinhalt durch Punktion, Drainage oder Abszeßexzision ist entscheidend für die Erregeridentifikation. Eine alleinige Chemotherapie zur Abszeßbehandlung wird nur angewandt, wenn 1. multiple, tief gelegene und/oder sehr kleine Abszesse vorliegen oder 2. sich der Patient in einem so schlechten Allgemeinzustand befindet, daß ihm ein invasiver Eingriff nicht zugemutet werden kann oder 3. eine Hirnphlegmone und kein abgekapselter Abszeß vorliegt. Gebräuchliche operative Verfahren sind die Abszeßaspiration (meist nach stereotaktischer Abszeßpunktion), die offene Kraniotomie mit Abszeßexzision und die offene Abszeßevakuation ohne Kapselentfernung. Für die ungezielte Chemotherapie vor Erregernachweis bevorzugen wir die Kombination von Cefotaxim (3×2–4 g/d i.v.) mit Metronidazol (3–4×0,5 g/d i.v.). Kortikosteroide sind indiziert, wenn der Prozeß raumfordernd ist und eine Herniation droht oder multiple Abszesse vorliegen, die nur teilweise operativ angehbar sind, oder Hirnregionen mit besonderer Ödemneigung betroffen sind.

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