PMID- 31074095
OWN - NLM
STAT- MEDLINE
DCOM- 20210222
LR  - 20211204
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 121
IP  - 1
DP  - 2020 Jan
TI  - miRNA expression profiling uncovers a role of miR-302b-3p in regulating skin 
      fibroblasts senescence.
PG  - 70-80
LID - 10.1002/jcb.28862 [doi]
AB  - Numbers of emerging evidence suggest that variable microRNA (miRNA) expression 
      facilitates the aging process. In this study, we distinguished aberrant miRNA 
      expression in aged skin and explored the biological functions and potential 
      mechanism of upregulated miR-302b-3p. At first, miRNA microarray analysis was 
      examined to explore miRNA expression profiling in the skin of aging mice model by 
      D-galactose (d-gal) injection. We identified 29 aberrant miRNAs in aged mice 
      skin. Next, KEGG enrichment analysis was conducted with DIANA-miPath v3.0, which 
      was revealed that enrichment pathways involved in such processes as extracellular 
      matrix-receptor interaction, MAPK signaling pathway, and mammalian target of 
      rapamycin (mTOR) signaling pathway. The target genes of deregulated miRNAs were 
      predicted from four bioinformatic algorithms (miRDB, Targetscan, miRwalk, and 
      Tarbase). The interaction network of miRNAs and their targets were visualized 
      using Cytoscape software. As a result, we found that some hub genes (including 
      JNK2, AKT1/2/3, PAK7, TRPS1, BCL2L11, and IKZF2) were targeted by 12 potential 
      miRNAs (including miR-302b-3p, miR-291a-5p, miR-139-3p, miR-467c-3p, miR-186-3p, 
      etc.). Subsequently, we identified five upregulated miRNA via quantitative 
      polymerase chain reaction and all of them were confirmed increased significantly 
      in aged skin tissues compared with young control tissues. Among them, high 
      expression of miR-302b-3p was verified in both aged skin tissues and senescence 
      fibroblasts. Furthermore, miR-302b-3p mimic accelerated skin fibroblast 
      senescence and suppressed the longevity-associated gene Sirtuin 1(Sirt1) 
      expression, whereas miR-302b-3p inhibitor could delay skin fibroblast senescence 
      and contribute Sirt1 expression. In addition, we demonstrated that c-Jun 
      N-terminal kinase 2(JNK2) is a direct target of miR-302b-3p by a luciferase 
      reporter assay. An inverse correlation was verified in fibroblasts between 
      miR-302b-3p and JNK2. Most importantly, siRNA JNK2 confirmed that low expression 
      of JNK2 could accelerate fibroblasts senescence. In conclusion, our results 
      indicated that overexpressed miR-302b-3p plays an important biological role in 
      accelerating skin aging process via directly targeting JNK2 gene.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Tan, Jingyong
AU  - Tan J
AD  - Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, 
      Guangxi Medical University, Nanning, China.
FAU - Hu, Longyuan
AU  - Hu L
AD  - Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, 
      Guangxi Medical University, Nanning, China.
FAU - Yang, Xin
AU  - Yang X
AD  - Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, 
      Guangxi Medical University, Nanning, China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Department of Physiology, Guangxi Medical University, Nanning, China.
FAU - Wei, Canshen
AU  - Wei C
AD  - Department of Orthopedics, Eighth Affiliated Hospital, Guangxi Medical 
      University, Guigang, China.
FAU - Lu, Qing
AU  - Lu Q
AD  - Department of Physiology, Guangxi Medical University, Nanning, China.
FAU - Chen, Zhilin
AU  - Chen Z
AD  - Department of Orthopedics, Eighth Affiliated Hospital, Guangxi Medical 
      University, Guigang, China.
FAU - Li, Jing
AU  - Li J
AUID- ORCID: 0000-0003-0218-8169
AD  - Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education, 
      Guangxi Medical University, Nanning, China.
AD  - Department of Physiology, Guangxi Medical University, Nanning, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190509
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (MIRN302 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - X2RN3Q8DNE (Galactose)
SB  - IM
MH  - Algorithms
MH  - Animals
MH  - *Cellular Senescence
MH  - Computational Biology
MH  - Down-Regulation
MH  - Female
MH  - Fibroblasts/*cytology
MH  - Galactose/metabolism
MH  - Gene Expression Profiling
MH  - Gene Regulatory Networks
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*metabolism
MH  - Mitogen-Activated Protein Kinase 9/metabolism
MH  - Signal Transduction
MH  - Sirtuin 1/metabolism
MH  - Skin/*cytology
MH  - Software
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - c-Jun N-terminal kinase 2
OT  - cellular senescence
OT  - miR-302b-3p
OT  - skin aging
EDAT- 2019/05/11 06:00
MHDA- 2021/02/23 06:00
CRDT- 2019/05/11 06:00
PHST- 2018/12/11 00:00 [received]
PHST- 2019/02/13 00:00 [revised]
PHST- 2019/02/28 00:00 [accepted]
PHST- 2019/05/11 06:00 [pubmed]
PHST- 2021/02/23 06:00 [medline]
PHST- 2019/05/11 06:00 [entrez]
AID - 10.1002/jcb.28862 [doi]
PST - ppublish
SO  - J Cell Biochem. 2020 Jan;121(1):70-80. doi: 10.1002/jcb.28862. Epub 2019 May 9.