MALAT1 recruited the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin‐mediated degradation and participated in trophoblast migration and invasion

Abstract

This study aimed to investigate the mechanism by which MALAT1 regulates CRY2 expression and participates in trophoblast migration and invasion. Three patients with unexplained recurrent spontaneous abortion, four patients with missed abortion, and four women who underwent artificial miscarriages were enrolled in this study. Quantitative reverse-transcription polymerase chain reaction and western blot analysis were used to detect RNA and protein expression, respectively. Trophoblast migration and invasion were detected by wound-healing and transwell invasion assays. RNA pull-down and Co-IP assays were used to indicate the interaction between MALAT1 and FBXW7 or the interaction between FBXW7 and CRY2. The results showed significantly decreased MALAT1 expression in the villous specimens from the RSA patients relative to that in the villous specimens from the missed abortion patients and the normal villous specimens. MALAT1 promoted trophoblast cell migration and invasion by negatively regulating CRY2 protein expression. MALAT1 recruited FBXW7 to impair CRY2 protein stability. In conclusion, MALAT1 downregulation in trophoblasts might be related to miscarriage. MALAT1 may recruit the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin-mediated degradation and participate in trophoblast migration and invasion.

Gypsy retrotransposon‐derived maize lncRNA GARR2 modulates gibberellin response

“…LncRNA ubiquitin‐like plant homeodomain and really interesting new gene finger domain‐containing protein 1 ( UHRF1 ) protein‐associated transcript ( UPAT ) interacts with the E3 ubiquitin ligase UHRF1, which is important for the survival of colon tumor cells (Taniue et al., 2016). LncRNA metastasis‐associated lung adenocarcinoma transcript‐1 ( MALAT1 ) is associated with the E3 ubiquitin ligase F‐box and WD repeat domain‐containing 7 (FBXW7), and this interaction plays a role in trophoblast migration and invasion (Wu et al., 2021). Future study is warranted to address whether GARR2 influences the ubiquitination of ZmUPL1‐bound substrates in the GA response.…”

Ubiquitin ligases: guardians of mammalian development

“…The timing and depth of this trophoblast invasion is determined by the balance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) at the fetus-uterus interface 88 . CUL1, CUL4, and SMURF2 tightly control this balance through regulating MMP inhibitor protein abundance 88,[91][92][93] . If any of these E3s fail, embryonic development fails.…”

“…Interestingly, CUL1 can target multiple substrates to exert the same effects on trophoblast MMP expression. Besides regulating TIMP1/2 levels, the MMP pathway inhibitor cryptochrome 2 has recently been added to the list of CUL1 targets for ubiquitinmediated degradation 92,94 .…”

The functions of long noncoding RNAs on regulation of F-box proteins in tumorigenesis and progression

“…MALAT1 was identified to recruit FBXW7 to stimulate the degradation of CRY2 and regulate trophoblast invasion and migration ( 126 ). MALAT1 was significantly downregulated in glioma samples and associated with tumor grade, tumor size and Karnofsky Performance status in glioma patients ( 127 ).…”