ABHD11-AS1: An Emerging Long Non-Coding RNA (lncRNA) with Clinical Significance in Human Malignancies

Golla, Upendarrao; Sesham, Kishore; Dallavalasa, Siva; Manda, Naresh Kumar; Sambamoorthy, Unnam; Sanapala, Arun Kumar; Nalla, Sharada; Kondam, Susmitha; Kumar, Rajesh

doi:10.3390/ncrna8020021

Cited by 9 publications

(6 citation statements)

References 100 publications

(186 reference statements)

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“…The intracellular domain of ACE2 preferentially formed an immune complex with the GTP-bound, endogenous Ras, which can become formed in the presence of excessive GTP (Figure 4B). Similar results were obtained in the case of the interaction with endogenous Ras downstream effectors phosphoinositide 3-kinase α and β (Figure S4; Figure S5), which are known to be direct upstream regulators of Akt kinase [19][20][21][24][25][26][27]. Taken together with the above results, it is suggested that Ras and the Ras signaling complex can be trapped to ACE2.…”

Section: Ace2 Preferentially Interacts With An Active Gtp-bound Ras T...supporting

confidence: 85%

CRISPR/CasRx-Mediated RNA Knockdown Reveals That ACE2 Is Involved in the Regulation of Oligodendroglial Cell Morphological Differentiation

Kato

Tago

Fukatsu

et al. 2022

ncRNA

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Angiotensin-converting enzyme 2 (ACE2) plays a role in catalyzing angiotensin II conversion to angiotensin (1–7), which often counteracts the renin-angiotensin system. ACE2 is expressed not only in the cells of peripheral tissues such as the heart and kidney, but also in those of the central nervous system (CNS). Additionally, ACE2 acts as the receptor required for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), whose binding leads to endocytotic recycling and possible degradation of the ACE2 proteins themselves. One of the target cells for SARS-CoV-2 in the CNS is oligodendrocytes (oligodendroglial cells), which wrap neuronal axons with their differentiated plasma membranes called myelin membranes. Here, for the first time, we describe the role of ACE2 in FBD-102b cells, which are used as the differentiation models of oligodendroglial cells. Unexpectedly, RNA knockdown of ACE2 with CasRx-mediated gRNA or the cognate siRNA promoted oligodendroglial cell morphological differentiation with increased expression or phosphorylation levels of differentiation and/or myelin marker proteins, suggesting the negative role of ACE2 in morphological differentiation. Notably, ACE2′s intracellular region preferentially interacted with the active GTP-bound form of Ras. Thus, knockdown of ACE2 relatively increased GTP-bound Ras in an affinity-precipitation assay. Indeed, inhibition of Ras resulted in decreasing both morphological differentiation and expression or phosphorylation levels of marker proteins, confirming the positive role of Ras in differentiation. These results indicate the role of ACE2 itself as a negative regulator of oligodendroglial cell morphological differentiation, newly adding ACE2 to the list of regulators of oligodendroglial morphogenesis as well as of Ras-binding proteins. These findings might help us to understand why SARS-CoV-2 causes pathological effects in the CNS.

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Section: Ace2 Preferentially Interacts With An Active Gtp-bound Ras T...supporting

confidence: 85%

CRISPR/CasRx-Mediated RNA Knockdown Reveals That ACE2 Is Involved in the Regulation of Oligodendroglial Cell Morphological Differentiation

Kato

Tago

Fukatsu

et al. 2022

ncRNA

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“…Not much is known on the function of long non-coding RNA (lncRNA) Abhd11os ( 139 ) in astrocytes. The human homolog ABHD11 antisense RNA 1 (ABHD11-AS1) was found to be highly expressed in gastric, lung, breast, colorectal, thyroid, pancreas, ovary, endometrium, cervix, and bladder cancer and was therefore suggested as biomarker for diagnosis and prognosis ( 140 ). In mouse models of Huntington's disease, expression of Abhd11os was reduced ( 139 ) or dysregulated ( 141 ) and its overexpression had neuroprotective effects in mice against mutant huntingtin-induced toxicity ( 139 ).…”

Section: Discussionmentioning

confidence: 99%

Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes

Roggan

Kronenberg

Wollert

et al. 2023

Front. Public Health

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IntroductionExposure to space conditions during crewed long-term exploration missions can cause several health risks for astronauts. Space radiation, isolation and microgravity are major limiting factors. The role of astrocytes in cognitive disturbances by space radiation is unknown. Astrocytes' response toward low linear energy transfer (LET) X-rays and high-LET carbon (12C) and iron (56Fe) ions was compared to reveal possible effects of space-relevant high-LET radiation. Since astronauts are exposed to ionizing radiation and microgravity during space missions, the effect of simulated microgravity on DNA damage induction and repair was investigated.MethodsPrimary murine cortical astrocytes were irradiated with different doses of X-rays, 12C and 56Fe ions at the heavy ion accelerator GSI. DNA damage and repair (γH2AX, 53BP1), cell proliferation (Ki-67), astrocytes' reactivity (GFAP) and NF-κB pathway activation (p65) were analyzed by immunofluorescence microscopy. Cell cycle progression was investigated by flow cytometry of DNA content. Gene expression changes after exposure to X- rays were investigated by mRNA-sequencing. RT-qPCR for several genes of interest was performed with RNA from X-rays- and heavy-ion-irradiated astrocytes: Cdkn1a, Cdkn2a, Gfap, Tnf, Il1β, Il6, and Tgfβ1. Levels of the pro inflammatory cytokine IL-6 were determined using ELISA. DNA damage response was investigated after exposure to X-rays followed by incubation on a 2D clinostat to simulate the conditions of microgravity.ResultsAstrocytes showed distinct responses toward the three different radiation qualities. Induction of radiation-induced DNA double strand breaks (DSBs) and the respective repair was dose-, LET- and time-dependent. Simulated microgravity had no significant influence on DNA DSB repair. Proliferation and cell cycle progression was not affected by radiation qualities examined in this study. Astrocytes expressed IL-6 and GFAP with constitutive NF-κB activity independent of radiation exposure. mRNA sequencing of X-irradiated astrocytes revealed downregulation of 66 genes involved in DNA damage response and repair, mitosis, proliferation and cell cycle regulation.DiscussionIn conclusion, primary murine astrocytes are DNA repair proficient irrespective of radiation quality. Only minor gene expression changes were observed after X-ray exposure and reactivity was not induced. Co-culture of astrocytes with microglial cells, brain organoids or organotypic brain slice culture experiments might reveal whether astrocytes show a more pronounced radiation response in more complex network architectures in the presence of other neuronal cell types.

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“…ABHD11-AS1, an important promoter in human malignancies, is located at 7q11.23 and is known as the long intergenic non-coding RNA 35 (LINC00035) and Williams–Beuren syndrome chromosome region 26 (WBSCR26) RNA gene. A number of studies in recent years have shown that ABHD11-AS1 is a potential biomarker for early diagnosis of CC ( Golla et al, 2022 ). Zhu et al (2022 ) observed increased lncRNA ABHD11-AS1 and decreased miR-1254 in the serum of CC patients compared with healthy controls, suggesting that dysregulation of ABHD11-AS1 and miR-1254 is involved in CC progression.…”

Section: Mechanisms Relating To Lncrnas In CCmentioning

confidence: 99%

The mechanisms and diagnostic potential of lncRNAs, miRNAs, and their related signaling pathways in cervical cancer

Sun

Song

et al. 2023

Front. Cell Dev. Biol.

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Cervical cancer (CC), the fourth most prevalent type of cancer among women worldwide, is associated with high rates of morbidity and mortality. Due to the long period of latency in CC, most patients are already in the middle to late stages when initially diagnosed, which greatly reduces the clinical cure rate and quality of survival, thus resulting in poor outcomes. In recent years, with continuous exploration in the fields of bioinformatics and molecules, it has been found that ncRNAs, including miRNAs and lncRNAs, without the ability to translate proteins are capable of activating or inhibiting certain signaling pathways by targeting and modulating the level of expression of proteins involved in these signaling pathways. ncRNAs play important roles in assisting with diagnosis, drug administration, and prediction of prognosis during CC progression. As an entry point, the mechanisms of interaction between miRNAs, lncRNAs, and signaling pathways have long been a focus in basic research relating to CC, and numerous experimental studies have confirmed the close relationship of miRNAs, lncRNAs, and signaling pathways with CC development. Against this background, we summarize the latest advances in the involvement of lncRNA- and miRNA-related signaling pathways in the development of CC to provide guidance for CC treatment.

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ABHD11-AS1: An Emerging Long Non-Coding RNA (lncRNA) with Clinical Significance in Human Malignancies

Cited by 9 publications

References 100 publications

CRISPR/CasRx-Mediated RNA Knockdown Reveals That ACE2 Is Involved in the Regulation of Oligodendroglial Cell Morphological Differentiation

CRISPR/CasRx-Mediated RNA Knockdown Reveals That ACE2 Is Involved in the Regulation of Oligodendroglial Cell Morphological Differentiation

Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes

The mechanisms and diagnostic potential of lncRNAs, miRNAs, and their related signaling pathways in cervical cancer

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