DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

Zhao, Haichao; Chen, Changzhou; Song, Huangqin; Qin, Rongyi; Wang, Xiaoxiao; He, Qizu; Li, Feng; Zhao, Hongguang; Li, Yanjun

doi:10.1155/2022/4277254

Cited by 6 publications

(5 citation statements)

References 37 publications

(41 reference statements)

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“…TOP IIα is related to cancer cell growth, invasion, and metastasis. 28 TOP IIα is revealed to correlate with higher Gleason scores, higher levels of preoperative PSA and shorter biochemical recurrence-free survival in prostate cancer patients. 29 In contrast, TOP IIβ is also expressed in nondividing F I G U R E 7 Effect of WC-A derivatives on DNA repair-related proteins.…”

Section: Discussionmentioning

confidence: 97%

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Mechanistic study of dual‐function inhibitors targeting topoisomerase II and Rad51‐mediated DNA repair pathway against castration‐resistant prostate cancer

et al. 2023

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BackgroundCastration‐resistant prostate cancer (CRPC) is refractory to hormone treatment and the therapeutic options are continuously advancing. This study aims to discover the anti‐CRPC effects and underlying mechanisms of small‐molecule compounds targeting topoisomerase (TOP) II and cellular components of DNA damage repair.MethodsCell proliferation was determined in CRPC PC‐3 and DU‐145 cells using anchorage‐dependent colony formation, sulforhodamine B assay and flow cytometric analysis of CFSE staining. Flow cytometric analyses of propidium iodide staining and JC‐1 staining were used to examine the population of cell‐cycle phases and mitochondrial membrane potential, respectively. Nuclear extraction was performed to detect the nuclear localization of cellular components in DNA repair pathways. Protein expressions were determined using Western blot analysis.ResultsA series of azathioxanthone‐based derivatives were synthesized and examined for bioactivities in which WC‐A13, WC‐A14, WC‐A15, and WC‐A16 displayed potent anti‐CRPC activities in both PC‐3 and DU‐145 cell models. These WC‐A compounds selectively downregulated both TOP IIα and TOP IIβ but not TOP I protein expression. WC‐A13, WC‐A14, and WC‐A15 were more potent than WC‐A16 on TOP II inhibition, mitochondrial dysfunction, and induction of caspase cascades indicating the key role of amine‐containing side chain of the compounds in determining anti‐CRPC activities. Furthermore, WC‐A compounds induced an increase of γH2AX and activated ATR‐Chk1 and ATM‐Chk2 signaling pathways. P21 protein expression was also upregulated by WC‐A compounds in which WC‐A16 showed the least activity. Notably, WC‐A compounds exhibited different regulation on Rad51, a major protein in homologous recombination of DNA in double‐stranded break repair. WC‐A13, WC‐A14, and WC‐A15 inhibited, whereas WC‐A16 induced, the nuclear translocation of Rad51.ConclusionThe data suggest that WC‐A compounds exhibit anti‐CRPC effects through the inhibition of TOP II activities, leading to mitochondrial stress‐involved caspase activation and apoptosis. Moreover, WC‐A13, WC‐A14, and WC‐A15 but not WC‐A16 display inhibitory activities of Rad51‐mediated DNA repair pathway which may increase apoptotic effect of CRPC cells.

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Section: Discussionmentioning

confidence: 97%

“…TOP IIα and TOP IIβ are two subclasses of TOP II. TOP IIα is related to cancer cell growth, invasion, and metastasis 28 . TOP IIα is revealed to correlate with higher Gleason scores, higher levels of preoperative PSA and shorter biochemical recurrence‐free survival in prostate cancer patients 29 .…”

Section: Discussionmentioning

confidence: 99%

Mechanistic study of dual‐function inhibitors targeting topoisomerase II and Rad51‐mediated DNA repair pathway against castration‐resistant prostate cancer

et al. 2023

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“…A study revealed that miR-22-5p downregulation contributed to the malignant progression of non-small-cell lung cancer by targeting transcription factor TWIST2 [53]. miR-22-5p may also inhibit tumor progression by sponging DNA topoisomerase II-alpha [54].…”

Section: Microrna 22-5pmentioning

confidence: 99%

Topology and Dynamics of Transcriptome (Dys)regulation

Planat,

Chester

2024

Preprint

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RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let’s delve into the mathematical intricacies of these sequences. We’ve previously devised a mathematical approach for defining a “healthy” sequence (10.14218/GE.2023.00079). This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt−1, it must be aperiodic, fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let’s explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI equation (10.3390/dynamics4010001). In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a “wild” dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find applications in cancer research.

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confidence: 99%

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”

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confidence: 99%

Retracted: DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

2023

Oxidative Medicine and Cellular Longevity

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DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

Cited by 6 publications

References 37 publications

Mechanistic study of dual‐function inhibitors targeting topoisomerase II and Rad51‐mediated DNA repair pathway against castration‐resistant prostate cancer

Mechanistic study of dual‐function inhibitors targeting topoisomerase II and Rad51‐mediated DNA repair pathway against castration‐resistant prostate cancer

Topology and Dynamics of Transcriptome (Dys)regulation

Retracted: DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

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