FOXM1/LINC00152 feedback loop regulates proliferation and apoptosis in rheumatoid arthritis fibroblast-like synoviocytes via Wnt/β-catenin signaling pathway

Abstract

Rheumatoid arthritis (RA), a chronic systemic disease, is featured with inflammatory synovitis, which can lead to destruction on bone and cartilage and even cause disability. Emerging studies demonstrated that Fibroblast-like synoviocytes (FLS) is a vital cellular participant in RA progression. Long non-coding RNAs (lncRNAs) are also reported to participate in the pathogenesis of RA. In our present study, lncRNA microarray analysis was applied to screen out lncRNAs differentially expressed in RA FLS. Among which, cytoskeleton regulator RNA (LINC00152) presented biggest fold change. Gain- or loss-of function assays were further carried out in RA FLS, and the results revealed that LINC00152 promoted proliferation but induced apoptosis in RA FLS. Furthermore, up-regulation of LINC00152 may induce promotion of Wnt/β-catenin signaling pathway in RA FLS. Mechanistically, we found that forkhead box M1 (FOXM1) transcriptionally activated LINC00152 in RA FLS. Additionally, LINC00152 positively regulated FOXM1 via sponging miR-1270. In conclusion, the present study focused on elucidating the function of FOXM1/LINC00152 positive feedback loop in RA FLS and its association with Wnt/β-catenin signaling.

LINC00152 promotes Ovarian tumor progression and Predicts Poor Prognosis by inhibiting the ubiquitination of BCL6

“…The previous studies have found that LINC00152 could compete as a ceRNA with miRs to fulfil its functions in hepatic and cervical cancers [11,15,30,31] . Besides, LINC00152 is related to the regulation of signaling pathways such as Wnt/β-Catenin pathway [12,32] . In contrast, Our MS/LS data based on RNA-pulldown assays and in vitro experiments suggested that oncogenic BCL6 was the posttranslational regulation target of LINC00152, and LINC00152 promoted ovarian tumor invasion and metastasis in a BCL6-mediated manner.…”

“…Other studies have got similar findings in gastric cancer [10] and hepatic carcinoma [11] , suggesting that LINC00152 might serve as a powerful oncogenic lncRNA in somatic malignancies. Researchers have found that LINC00152 forms the loop feedback with FOXM1 to stimulate tumor growth [12] and might serve as the ceRNA (competing endogenous RNA) to regulate miRNAs to fulfil its biological functions [5,13,14] . Although the impact of LINC00152 on ovarian cancer proliferation has been implicated recently [15] , its role and the exact molecular mechanism to regulate the ovarian tumor behavior need further investigation.…”

Involvement of long noncoding RNAs in the pathogenesis of autoimmune diseases

“…In addition, FER1L4 regulates inflammation in RA FLSs by potentially targeting NLRC5 [ 79 ]. Several lncRNAs, including MALAT1 [ 80 ], UCA1 [ 81 ], DILC [ 82 ], LncIL7R [ 83 ] and LINC00152 [ 84 ], have been reported to contribute to apoptosis and proliferation in RA-FLSs. lncRNA GAS5 [ 85 , 86 ] and ITSN1-2 [ 87 ] are implicated in apoptosis and inflammation in RA FLSs.…”

“… [ 80 ] UCA1 Human FLS Down-regulated Induces apoptosis by Wnt6 [ 81 ] DILC Human FLS, plasma Down-regulated Regulates apoptosis and IL-6 expression. [ 82 ] Lnc-IL7R Human FLS – Promotes growth of RA FLS through interaction with EZH2 [ 83 ] LINC00152 Human FLS Up-regulated Regulates proliferation and apoptosis via Wnt/beta-catenin signaling pathway [ 84 ] GAS5 Human Tanshinone IIA -treated FLS, plasma Down-regulated Responsible for apoptosis and IL-18 expression. [ 85 , 86 ] ITSN1-2 Human FLS Up-regulated Regulates apoptosis, proliferation and inflammation by NOD2/RIP2 pathway.…”

“… [ 87 ] PVT1 Rat FLS Up-regulated Regulates inflammation response and apoptosis. [ 90 ] MEG3 Rat FLS Down-regulated Modulates inflammation by targeting NLRC5 [ 88 ] MEG3 Human FLS, chonroncyte Down-regulated Inhibit proliferation and inflammation by miR-141 and AKT/mTOR pathway [ 84 ] C5T1lncRNA Human Various tissues, PBMC Up-regulated Influences the transcript levels of C5. [ 71 ] NR024118 Mouse FLS Up-regulated Regulates inflammation response.…”