PMID- 35426182 OWN - NLM STAT- MEDLINE DCOM- 20220517 LR - 20220716 IS - 1098-2825 (Electronic) IS - 0887-8013 (Print) IS - 0887-8013 (Linking) VI - 36 IP - 5 DP - 2022 May TI - MALAT1 regulates PCT expression in sepsis patients through the miR-125b/STAT3 axis. PG - e24428 LID - 10.1002/jcla.24428 [doi] LID - e24428 AB - BACKGROUND: Procalcitonin (PCT) is an important marker in diagnosing sepsis. However, some other diseases can also cause an increase in PCT. PCT still has some limitations in the clinical application of diagnosing sepsis. Therefore, it is of great significance to clarify the regulatory mechanism of PCT expression in sepsis and provide new therapeutic targets for sepsis. METHODS: Blood samples from clinical patients were collected, and peripheral blood monocytes were isolated. Bioinformatics was performed to find the ceRNA regulatory network of STAT3/PCT. MALAT1 and miR-125b were detected by qRT-PCR. MALAT1 was located by fluorescence in situ hybridization (FISH) in U937 cells, and the regulatory relationship between MALAT1, miR-125b, and STAT3 was verified by double luciferase activity report and RNA pull-down assay. U937 cells were transfected with miR-125b, and the effects of the MALAT1/miR-125b/STAT3 pathway on gene and protein secretion levels of PCT were verified by qRT-PCR, western blot, and ELISA. RESULTS: In the serum of sepsis patients and lipopolysaccharide(LPS)-induced U937 cells, MALAT1, STAT3, and PCT gene expression levels were significantly increased, while miR-125b expression level was decreased. FISH results showed that the MALAT1 transcript was mainly located in the nucleus. The double luciferase activity report and RNA pull-down assay results suggested a targeted regulatory relationship between MALAT1, miR-125b, and STAT3. LPS-induced U937 cells transfection with MALAT1 siRNA decreased STAT3 protein expression and phosphorylation level and the expression of PCT. Co-transfection with miR-125b inhibitor effectively reversed this phenomenon. CONCLUSIONS: MALAT1 could upregulate the expressions of STAT3 and PCT by targeted adsorption of miR-125b. CI - (c) 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC. FAU - Le, Yuanjie AU - Le Y AD - Department of Emergency, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China. AD - Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China. FAU - Shi, Yongwei AU - Shi Y AUID- ORCID: 0000-0001-5673-217X AD - Department of Emergency, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo, China. AD - Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China. LA - eng GR - 2022-F16/Ningbo Key Support Medical Discipline/ GR - 2020ky839/Medical health Science and Technology project of Zhejiang Province/ PT - Journal Article DEP - 20220415 PL - United States TA - J Clin Lab Anal JT - Journal of clinical laboratory analysis JID - 8801384 RN - 0 (Lipopolysaccharides) RN - 0 (MALAT1 long non-coding RNA, human) RN - 0 (MIRN125 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Procalcitonin) RN - 0 (RNA, Long Noncoding) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) SB - IM MH - Humans MH - In Situ Hybridization, Fluorescence MH - Lipopolysaccharides MH - *MicroRNAs/genetics MH - *Procalcitonin/metabolism MH - *RNA, Long Noncoding/genetics MH - STAT3 Transcription Factor/genetics/metabolism MH - *Sepsis/genetics PMC - PMC9102486 OTO - NOTNLM OT - MALAT1 OT - STAT3 OT - miR-125b OT - procalcitonin OT - sepsis COIS- The authors declare that they have no competing interests. EDAT- 2022/04/16 06:00 MHDA- 2022/05/18 06:00 PMCR- 2022/04/15 CRDT- 2022/04/15 05:34 PHST- 2022/02/24 00:00 [revised] PHST- 2021/12/17 00:00 [received] PHST- 2022/03/02 00:00 [accepted] PHST- 2022/04/16 06:00 [pubmed] PHST- 2022/05/18 06:00 [medline] PHST- 2022/04/15 05:34 [entrez] PHST- 2022/04/15 00:00 [pmc-release] AID - JCLA24428 [pii] AID - 10.1002/jcla.24428 [doi] PST - ppublish SO - J Clin Lab Anal. 2022 May;36(5):e24428. doi: 10.1002/jcla.24428. Epub 2022 Apr 15.