The Genes Associated with RNA Editing and Glioma on the Chromosome 22q

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The Genes Associated with RNA Editing and Glioma on the Chromosome 22q G. Wang1, Y. Tian1 Department of Neurosurgery, China-Japan Union Hospital, Jilin University Changchun, 130033, China 1

tianyu2801@126.com

*1

Abstract It is well known that RNA editing plays a critical role in glioma progress. The most frequent RNA editing mechanism is controlled by the ADAR (adenosine deaminase acting on dsRNA) family of enzymes. The recent researches proved that there is a great quantity of new ADAR editing sites in 1637 kinds of genes. Whether these genes connect with RNA editing or ADAR on glioma is still unknown. To clarify the possibility of those genes connect with RNA editing on glioma, we arrange those genes according to the most frequent chromosome imbalances in primary glioma, which suggests that most of those genes are concentrated on chromosome 22q. Furthermore, there are 8 genes (TXNRD2, ADRBK2, THOC5, APOL1, APOL6, PISD, ARSA and GGA1) associated with glioma, meanwhile, 3 genes (ADRBK2, THOC5 and APOL1) associated with gene transcription, and the TXNRD2 associated with post-transcription regulation in human medulloblastoma cells. On the other hand, 8 genes (APOBEC3D, POLDIP3, SAPS2, GNB1L, FLJ23588, DMC1, NUP50 and POLR2F ) are associated with RNA composition, although without connection with glioma. At present, none of them is reported to be associated with RNA editing or ADAR on glioma. Overall, those 16 genes which may have connection with glioma or RNA composition, suggest the existence of new ADAR editing sites which are potential candidates in charge of RNA editing on glioma.

Keywords RNA Editing; Glioma; Chromosome 22q

Introduction RNA editing plays a critical role in tumor(glioma included) progress. The most frequent RNA editing mechanism in mammals involves the conversion of specific adenosines into inosines (A-to-I) by the ADAR (adenosine deaminase acting on dsRNA) family of enzymes. Levanon EY researches proved that 12,723 new A-to-I editing sites in 1,637 different genes. We arrange those genes according to site of the most frequent mutation in primary glioma. Then it is found that the most concentrated place is chromosome 22q (29 genes). Here our summary is reported in the following part:

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8 Genes Associated with Glioma TXNRD2 TXNRD2, i.e. Thioredoxin reductase 2 (TrxR2), SELZ, TR, TR-BETA, TR3, TRXR2, selenoprotein Z; thioredoxin reductase 3 and thioredoxin reductase beta, is on the chromosome 22q11.21.

As an isoenzyme of TrxR, which is both the major component in gradient of the hydrosulfide group regulation system and the essential material for the oxidation-reduction reaction in the cell metabolism, its saitivity to active oxygen makes itself an essential enzyme on the oxidation-reduction reaction in tumor cell. And its overexpression in most mankind tumor tissue also makes itself a resistance marker or target in the anti-tumor drug research.

TXNRD2 can induce the apoptosis in HeLa (human), Neuro2A (mouse) and COS-7 (monkey). Monden T proves that thyroid hormone T3 can regulate the TR level after the RNA composition process in the human medulloblastoma HTB-185.

ADRBK2 ADRBK, i.e. Adrenergic beta receptor kinase 2, BARK2, GRK3 and beta adrenergic receptor kinase 2, is on the chromosome 22q12.1.

Some literatures reported association between β2adrenergic receptors (β2AR) or β-adrenergic receptor (β-AR) and glioma. Among the β2-adrenergic receptors, β-adrenergic receptor and protein kinase C (PKC), there are regulating effects in the rat glioma C6 cell, which is associated with gene transcription.

THOC5 THOC5, i.e. THO complex 5, NF2/meningioma region protein pK1.3, C22orf19, Fmip, PK1.3, Fms-interacting protein (FMIP) and placental protein 39.2, is located on the chromosome 22q12.2.

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The THOC5 gene plays an critical role in the process of exporting mRNA from cell nucleus to cytolymph. And there is a low THOC5 expression in the glioma patient.

The GGA1 gene over-expression can assist ceramide to induce tumor cell apoptosis in the mouse glioma C6 cell.

APOL1

8 Genes Associated with RNA Composition yet without Glioma

APOL1, i.e. Apolipoprotein L1, APO-L, APOL, APOLI, OTTHUMP00000028705, apolipoprotein L-I and apolipoprotein L1, is on the chromosome 22q13.1.

The apoL family proteins associated with lipid transportation and metabolism, having the same construction and function as the Bcl-2 family proteins are used on the cell envelope ion channel to participate in inducing apoptosis. The apolipoprotein L is associated with the alpha-lipoprotein transport in human blood serum as well with schizophrenia.

APOL6 APOL6, i.e. Apolipoprotein L 6; APOL-VI, DKFZp667M075, FLJ38562, FLJ90164, MGC57495, apolipoprotein L-VI and apolipoprotein L6, is on the chromosome 22q12.3.

The ApoL6 gene is associated with malignant cell apoptosis. Liu Z et al found that the ApoL6 product has homologisation similarity to the Bcl-2 family members. It can be cloned and functionally expressed in the colorectal cancer cell. The over-expression of the ApoL6 gene induces mitochondria-mediated apoptosis in cancer cell .

PISD PISD, i.e. Phosphatidylserine decarboxylase, DJ858B16, KFZP566G2246, PSSC and dJ858B16.2, is on the chromosome 22q12.2.

The PISD gene adjusts the balance of phosphatide metabolism in the glioma C6 cell.

ARSA ARSA, i.e. Arylsulfatase A, MLD and metachromatic leucodystroph,on the chromosome 22q13.33.

Nakahara Y et al detected that the ARSA gene has certainly effective in the process of tumor generation and development in the malignant glioma through gene array analyzing biopsy organization.

GGA1 GGA1, i.e. Golgi associated, gamma adaptin ear containing, ARF binding protein 1, ADP-ribosylation factor binding protein 1 , OTTHUMP00000028975, OTTHUMP00000042200 and gamma-adaptin related protein 1, is on the chromosome 2q13.31.

APOBEC3D APoBEC3D, i.e. Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3D, ARP6 and catalytic polypeptide-like 3D, is on the chromosome 22q13.1-q13.2.

The apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) families include APOBEC3A, APOBEC3B, APOBEC3C, APOBEC3D, APOBEC3E, APOBEC3F and APOBEC3G. APOBEC3D is the member of the APOBEC3 family. APOBEC3 could inhibit the copy of mouse mammary tumor virus (MMTV).

POLDIP3 POLDOP3, i.e. Polymerase (DNA-directed), delta interacting protein 3, KIAA1649, IP46, SKAR, DNA polymerase delta interacting protein 3, OTTHUMP00000028521, RNA-binding protein P46, S6K1 Aly/REF-like target and polymerase delta interacting protein 46, is on the chromosome 22q13.2.

The POLDIP3 gene can be expressed in the different mammalian tissue, participating in the cell growth control. The phosphorylation process of S6K1 manipulates the cell cycle, and associates with the PremRNA shearing and mRNA export during translation and transcription. Association between POLDIP3 and glioma has not been reported yet.

SAPS2 SAPS2, i.e. SAPS domain family, member 2,KIAA0685 and SAP190, is on the chromosome 22q13.33.

Some literatures report that SAP190 controls the process of gene information transcription and translation during G1 phase.

GNB1L GNB1L, i.e. Guanine nucleotide binding protein (G protein), beta polypeptide 1-like, WDR14, DGCRK3, FKSG1, GY2, KIAA1645, WDVCF, G-protein beta subunit-like protein and guanine nucleotide binding protein beta-subunit-like polypeptide, is on the chromosome 22q11.2.

GNB1L is associated with the intracellular process of

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RNA composition, mental disorder and some diseases in the pars encephalica.

FLJ23588 FLJ23588, i.e. CAP-binding protein complex interacting protein 1, DJBP, HSCBCIP1, KIAA1672, dJ185D5.1 and OTTHUMP00000028872, is on the chromosome 22q13.1-q13.33.

JBP is a new DJ-1 protein, which can express obviously in the testicle, and could interfere with the androgen receptor protein transcription.

DMC1 DMC1, i.e. DMC1 dosage suppressor of mck1 homolog, meiosis-specific homologous recombination, DMC1H, HsLim15, LIM15, MGC150472, MGC150473, dJ199H16.1, disrupted meiotic cDNA1 and meiotic recombination protein DMC1/LIM15 homolog, is on the chromosome 22q13.1.

In human body, the interaction between RAD51 and DMC1 happens in the meiophase as MSH4 in the budding fungus. And the 2 genes complete homologization through DNA double strands exchange.

NUP50 NUP50, i.e. Nucleoporin 50kDa, MGC39961, NPAP60, NPAP60L, OTTHUMP00000028685 and nuclear poreassociated protein 60L, is on the chromosome 22q13.31.

The protein NUP50 expresses is nucleoporin which is an important transport protein on the nuclear pore, too. When NUP50 gene expression deletion happens, P27 gene could expression. When P27 is overexpressed, the cell growth might stay during G1 phase.

When NUP50 is over-expressed, P27 expression would descend.

APOL1, APOL6, PISD, ARSA and GGA1) associated with glioma, meanwhile, 3 genes (ADRBK2, THOC5 and APOL1) associated with gene transcription, and the TXNRD2 associated with post-transcription regulation in human medulloblastoma cells. On the other hand, 8 genes (APOBEC3D, POLDIP3, SAPS2, GNB1L, FLJ23588, DMC1, NUP50 and POLR2F) are associated with RNA composition, although without connection with glioma. So in summary, the literature search suggests that those 16 genes which may have connection with glioma or RNA composition, indicate the existence of new ADAR editing sites which are potential candidates in charge of RNA editing on glioma.

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G. Wang received the bachelor degrees with life science and medicine from Jilin University, Changchun, China, in 2007 and 2009 respectively. After receiving the Master degree of medicine from Bethune 1st Hospital of Jilin University, Changchun, China, in 2011, he became a Ph.D. candidate in Chirurgery from China-Japan Union Hospital of Jilin University, Changchun, China, in 2012. G. Wang reasearch interests are glioma genetic therapy.

In 2011, he became an intern doctor in Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Jilin University, China.

Dr. Yu Tian received the Bachelor and Master degrees with medicine from Jilin Medical College and Second Hospital of BETHNUE Medical School, China in 1990 and 1996 respectively. He received the Ph.D. degree in Oncologyimmunology from Jilin University Medical Center, China, in

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International Journal of Advance in Medical Science (AMS) Volume 2, 2014

2002. From 2003.8 to 2005.12, he has made his Post-Dr research in Department of Neurosurgery of Peking Union Medical College Hospital, China. From 2008.4 to 2008.11, he has finished his Post-Dr research in Department of Neurosurgery of Medical University Vienna, Austria.

Dr. Yu Tian reasearch interests are Glioma operation and basic research. He published over 110 research papers.

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In 1990, he joined Department of Neurosurgery of the Second Hospital of BETHNUE Medical School in China as a doctor till 1996. In 1996, he became an attending doctor.

From 1999 to 2004, he worked as an Associate Professor.

Since 2004 to date, he has been a Professor in Department of Neurosurgery of the Third Hospital of Jilin University in China.