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Carney Complex
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The two supplemental criteria for CNC diagnosis are (i) affected first-degree relative, and (ii) inactivating mutation of the PRKAR1A gene or activating pathogenic variants of PRKACA (single base substitutions and copy number variation) and PRKACB [1,2].
Carney Complex
Published in Dongyou Liu, Tumors and Cancers, 2017
The two supplemental criteria are (i) affected first-degree relative and (ii) inactivating mutation of the PRKAR1A gene or activating pathogenic variants of PRKACA (single base substitutions and copy number variation) and PRKACB [1,2].
The research progress of circular RNAs in hematological malignancies
Published in Hematology, 2019
Tingting Ji, Qiuni Chen, Shandong Tao, Yuye Shi, Yue Chen, Li Shen, Chunling Wang, Liang Yu
Circ-DLEU2 was originated from DLEU2 locus which was shown to induce adult cancers and leukemogenesis. Wu et al. [8] revealed that the expression of circ-DLEU2 in AML bone marrow cells was higher than healthy controls, but there was no significantly statistical difference of circ-DLEU2 expression among different risk stratifications of AMLpatients. Mechanistically, circ-DLEU2 acted as a miRNA sponge to competitively inhibit the activity of miR-496 which played an antagonistic role in PRKACB-related AML cell proliferation and apoptosis. The PRKACB, a kind of protein which was needed in the cell growth process, was highly expressed in AML [28]. The PRKACB expression in AML cells was negatively associated with miR-496 and promoted by circ-DLEU2, thus accelerating the development of AML. Circ-DLEU2 might act as a diagnostic marker and AML therapeutic target via inhibiting the miR-496/PRKACB axis.
Involvement of long non-coding RNA HULC (highly up-regulated in liver cancer) in pathogenesis and implications for therapeutic intervention
Published in Expert Opinion on Therapeutic Targets, 2019
Christiane Klec, Tony Gutschner, Katrin Panzitt, Martin Pichler
Early mechanistic studies of the consequences of increased HULC expression in hepatocellular carcinoma demonstrate an involvement of cAMP response element-binding protein (CREB) which usually binds to and activates target promoters [29]. Wang et al. provide results of promoter binding and activity studies, demonstrating an existence of a CREB binding site in the HULC promoter region and that CREB is able to activate the HULC promoter and thus, can control HULC expression on transcriptional level. When inhibiting the CREB stimulator protein kinase A (PKA), phosphorylation of CREB is reduced resulting in inactive CREB. As a consequence, HULC promoter activity is diminished and HULC expression in Hep3B cells is drastically reduced. Further experiments show that HULC and miR-372 directly interact and that HULC acts as molecular sponge for the tumor suppressive miR-372 [30]. Reduced miR-372 levels may decrease repression of its mRNA targets resulting in increased CREB phosphorylation in HCC. Target mRNA database search results provide information that cAMP-dependent protein kinase catalytic subunit beta (PRKACB) mRNA is a target of miR-372. PRKACB is the gene coding for the β-catalytic subunit of PKA. In the non-tumor or physiological context miR-372 represses PRKACB translation resulting in reduced CREB phosphorylation and thus, reduced HULC promoter activity. In tumor tissue increased HULC levels sponge miR-372 resulting in increased PRKACB, augmented CREB phosphorylation and thus, also increased HULC promoter activity, representing an elegant feedback loop in HCC [31]. Du et al. demonstrate that Hepatitis B virus x protein (HBx) increases HULC expression via CREB-driven promoter activation. HULC promotes proliferation of stably transfected HBx cells and respective HULC knock-down leads to reduced proliferation, colony formation in vitro and decreased tumor volume, weight, and frequency in vivo by regulating the tumor suppressor p18 [32]. Hämmerle & Gutschner et al. identified another regulator of HULC in 2013, namely, insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [33]. This factor was shown to contribute to carcinogenesis by post-transcriptionally fine-tuning the expression of essential mRNA targets [34]. High IGF2BP1 levels are associated with poor prognosis of lung cancer and ovarian cancer patients [35,36]. IGF2BP1 specifically regulates HULC stability by mediating interaction between HULC and CCR4-NOT transcription complex subunit 1 (CNOT1) – a component of the CCR4-NOT deadenylase complex – ultimately leading to destabilization of HULC [33]. After the study of Wang et al. in 2010 where miR-372 was shown to be involved in HULC-associated HCC pathogenesis [31], the group of Wan et al. five years later demonstrated an involvement of another microRNA by showing that miR-203 down-regulates HULC and a disintegrin and metalloproteinase 9 (ADAM9) [37] and, thus, is controlling HCC progression [38]. Since then several miRNAs have been shown to play a role in HULC-associated HCC progression (Table 2) whereas HULC mostly functions as ceRNA (Figure 1).