Function of microRNA-346 and its Roles in Human Diseases

Jin-hua He and Yu-guang Li＊

Department of Laboratory,Panyu Center Hospital,Guangzhou 511400,China

MICRORNAs (miRNAs) are short (20-22 nucleotides),non-coding RNA molecules involved in the regulation of mRNAs by pairing with their 3'-untranslated region (3'-UTR) and affecting their stability or directing their silencing or degradation.1miRNAs are likely to play roles in most cellular processes,including proliferation,development,differentiation,and apoptosis.2People have made progress in the research of miRNA field,but the study about microRNA-346 (miR-346) is very little.This study used biological software to analyze the biological characters of miR-346,and further reviewed the function of miR-346 and its roles in human diseases.

Localization of miR-346 in the genomes of different species

We analyzed the position of miR-346 in different species by using University of California Santa Cruz (UCSC) Genome Browser and Ensembl genome online browsing tools.The results revealed miR-346 was located in the region between 86 429 909 and 864 300 034 of human chromosome 10,which encoded 52 mature miRNAs.The mature single strand miRNA molecular sequence was 5‘-GUGGCUGCACUCACUUCCUUC-3’ (Table 1).

Target gene of human miR-346

Since miRNA was found,expounding the function of miRNA has been the hot spot of the biomedical research.So far,a few function of miRNA has been known.Understanding the relations between miRNA and its target genes is the key for research miRNA function.We predicted the miRNA target genes using miRNA target gene analysis softwares,namely MicroCosm,miRanda,DIANA-microT,RNAhybrid,Target-Scan,and RNA22.Bioinformatics analysis showed low density lipoprotein receptor-related protein 6 (LRP6;Gene ID∶NM_005328) gene was the target gene of human miR-346.

Table 1.Location of miR-346 in the genomes of different species

Function of miR-346

Receptor-interacting protein 140 (RIP140) is a transcriptional co-repressor that regulates diverse genes such as those responsive to hormones and involved in metabolic processes.The expression of miR-346 enhances the gene repressive activity of RIP140.3Oskowitzet al4reported that miRNAs which regulate differentiation in a variety of simpler systems also regulate differentiation of human multipotent stromal cells (hMSCs) from bone marrow.The prediction was confirmed for two of the miRNAs,hsa-miR 199a and hsa-miR346,in which overexpression of the miRNAs decreased leukemia inhibitory factor secretion by hMSCs.The results demonstrate that differentiation of hMSCs might be regulated by miR-346,hsa-miR 199a,and target leukemia inhibitory factor.

Roles of miR-346 in carcinogenesis and other diseases

Weberet al5reported that both miR-197 and miR-346 contribute to follicular thyroid carcinogenesis.Both miRNAs and their target genes might be potential novel molecular markers of carcinomas and act as novel targets for interference treatment,which could potentially normalize the deregulated profile of many downstream target genes.

miRNAs have emerged as key players in the regulation of target mRNAs expression.They have been associated with diverse biological processes.Recent studies have demonstrated that miRNAs play a role in inflammatory responses.Alsalehet al6reported that miR-346 indirectly regulated interleukin-18 release by indirectly inhibiting lipopolysaccharide (LPS)-induced Bruton’s tyrosine kinase expression in LPS-activated rheumatoid arthritis fibroblastlike synoviocytes.These findings suggest that miRNAs functioning as regulators might help to fine-tune the inflammatory response in rheumatoid arthritis.Suiet al7described a comparison between miRNA expression profile of acute rejection and the controls.Through microarray analysis and quantitative real-time RT-PCR confirmation,they identified 20 miRNAs differently expressed in acute rejection after renal transplantation.Their data indicate that miR-346 is potentially involved in the pathogenesis of acute rejection.Zhuet al8used quantitative real-time PCR to determine the expression levels of miR-346 and glutamate receptor ionotropic delta 1 (GRID1) using brain RNA samples from the Stanley Array Collection.The results revealed the expressions of miR-346 and GRID1 were lower in schizophrenia patients than those in bipolar patients or in normal controls.This study implicates the importance of miR-346 in schizophrenia.Ilnytskyyet al9reported that altered miR-346 expression patterns in irradiated hematopoietic tissues,suggesting a sex-specific protective mechanism against radiation cytotoxicity.

In conclusion,miR-346 was highly conservative in different species.The predicted target gene of miR-346 was LRP6,which indicated miR-346 might play an important role in hyperlipidemia.miR-346 could contribute to follicular thyroid carcinogenesis and inflammatory responses,and so on.

1.Bartel DP.MicroRNAs∶target recognition and regulatory functions.Cell 2009;136∶215-33.

2.Bostjancic E,Glavac D.Importance of microRNAs in skin morphogenesis and diseases.Acta Dermatovenerol Alp Panonica Adriat 2008;17∶95-102.

3.Tsai NP,Lin YL,Wei LN.MicroRNA mir-346 targets the 5’-untranslated region of receptor-interacting protein 140(RIP140) mRNA and up-regulates its protein expression.Biochem J 2009;424∶411-8.

4.Oskowitz AZ,Lu J,Penfornis P,et al.Human multipotent stromal cells from bone marrow and microRNA∶regulation of differentiation and leukemia inhibitory factor expression.Proc Natl Acad Sci U S A 2008;105∶18372-7.

5.Weber F,Teresi RE,Broelsch CE,et al.A limited set of human MicroRNA is deregulated in follicular thyroid carcinoma.J Clin Endocrinol Metab 2006;91∶3584-91.

6.Alsaleh G,Suffert G,Semaan N,et al.Bruton's tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes.J Immunol 2009;182∶5088-97.

7.Sui W,Dai Y,Huang Y,et al.Microarray analysis of MicroRNA expression in acute rejection after renal transplantation.Transpl Immunol 2008;19∶81-5.

8.Zhu Y,Kalbfleisch T,Brennan MD,et al.A MicroRNA gene is hosted in an intron of a schizophrenia-susceptibility gene.Schizophr Res 2009;109∶86-9.

9.Ilnytskyy Y,Zemp FJ,Koturbash I,et al.Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism.Biochem Biophys Res Commun 2008;377∶41-5.