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LncRNA GASAL1 Interacts with SRSF1 to Regulate Trophoblast Cell Proliferation, Invasion, and Apoptosis Via the mTOR Signaling Pathway.

ABSTRACT: Long noncoding RNAs (lncRNAs) are crucial regulatory molecules involved in diverse biological processes and human diseases, including preeclampsia (PE). The lncRNA growth arrest associated lncRNA 1 (GASAL1) has been implicated in multiple malignant solid tumors and other diseases, while it is poorly known as the potential molecular mechanism of GASAL1 in PE. In this study, GASAL1 was significantly downregulated in the placentas' of tissues from primipara with PE and trophoblast cell lines. Then, the upregulation of GASAL1 dramatically decreased proliferation and invasion and enhanced apoptosis in HTR-8/SVneo and JAR cells. Bioinformatics tool predicated that there is a potential interaction between GASAL1 and serine/arginine splicing factor 1 (SRSF1). RNA pull-down assays showed that GASAL1 directly binds with SRSF1 that could promote cell proliferation and invasion and suppress cell apoptosis. Further research showed that promoting effects of trophoblasts proliferation and invasion caused by co-transfecting GASAL1 and SRSF1 into HTR-8/SVneo and JAR cells were impaired by SRSF1 knockdown. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity by rapamycin influenced the effects of GASAL1 on cell proliferation, invasion, and apoptosis. Taken together, these findings suggest that lncRNA GASAL1 interacts with SRSF1 to regulate the proliferative, invasive, and apoptotic abilities of trophoblast cells via the mTOR signaling pathway.

SUBMITTER: Liu J

PROVIDER: S-EPMC7784605 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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LncRNA GASAL1 Interacts with SRSF1 to Regulate Trophoblast Cell Proliferation, Invasion, and Apoptosis Via the mTOR Signaling Pathway.

Liu Jia J Zhang Qing Q Ma Nan N

Cell transplantation 20200101

Long noncoding RNAs (lncRNAs) are crucial regulatory molecules involved in diverse biological processes and human diseases, including preeclampsia (PE). The lncRNA growth arrest associated lncRNA 1 (GASAL1) has been implicated in multiple malignant solid tumors and other diseases, while it is poorly known as the potential molecular mechanism of GASAL1 in PE. In this study, GASAL1 was significantly downregulated in the placentas' of tissues from primipara with PE and trophoblast cell lines. Then, ...[more]

PMID: 33028104

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Project description:BackgroundPreeclampsia (PE) is a complex pregnancy-related disease that endangers the safety of maternal and fetal. The purpose of this study is to reveal the pathogenesis of preeclampsia and discover new predictors from the perspective of peptidomics. The umbilical cord blood of PE and control group was analyzed by peptidomics. A peptide named Regulation of Proliferation Process in Preeclampsia (ROPPIP) was screened out to explore its role in the proliferation, migration and apoptosis of trophoblast cells in preeclampsia.MethodsWe compared and analyzed the umbilical cord blood of patients with PE and normal pregnant women using liquid chromatography-tandem mass spectrometry (LC-MS). hTR-8/Svneo cells cultured in vitro were divided into ROPPIP group and a disordered peptide group as control. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to the expression of Matrix metalloproteinase-2 (MMP2), nuclear associated antigen Ki67, B-cell lymphoma-2 (Bcl2), Caspase 3, and β-actin protein.ResultsWe identified 133 differential peptides. Of these, 51 were up-regulated while 82 were down-regulated. the polypeptide SFGVRMATASPTDGNV with low differential expression in the serum of PE patients was selected for the study, we named the polypeptide as Regulation of Proliferation Process in PE (ROPPIP). The experiment shows that ROPPIP can up-regulate the expression levels of MMP2, Ki67, and Bcl2 in HTR-8/Svneo cells, down-regulate the expression of caspase-3, promote the proliferation and migration of HTR-8/Svneo cells and inhibit the apoptosis induced by cisplatin, the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway may be associated with the function of ROPPIP.ConclusionsROPPIP promotes HTR-8/Svneo cells migration and proliferation, and inhibits apoptosis, by regulating the activation of the PI3K/AKT/mTOR signaling pathway.

Project description:BackgroundLong non-coding RNAs (lncRNAs) are pervasively transcribed in genome and emerging as a new player in tumorigenesis due to their functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. As the most frequent malignancy and the foremost source of cancer mortality, lung cancer is a heterogeneous disorder. The most common type of lung cancer is Non-small cell lung cancer (NSCLC), occupying 85% of the total cases, and the main subtypes of NSCLC include lung adenocarcinoma (LAD), large cell carcinoma (LCC), and lung squamous cell carcinoma (LSCC). Recently, numerous lncRNAs have been reported to be strongly linked to NSCLC. In the present study, we found that a new lncRNA CBR3-AS1 is highly expressed in lung cancer. In addition, we also examined the expression of lncRNA CBR3-AS1 in 60 of LADs, 40 of LCCs and 40 of LSCCs patient samples, finding that CBR3-AS1 was specificity highly expressed in LAD cancer tissues. Mechanically, we discovered that CBR3-AS1 could regulate the proliferation, migration and invasion of LAD cells through targeting Wnt/β-catenin signaling.MethodsReal-time PCR, RNA-pulldown, RIP, western blotting, lentivirus transfection, luciferase reporter assays, cell proliferation assays, colony formation assays, wound healing scratch assays and transwell assays were employed to examine the relationship between lncRNA CBR3-AS1 and its regulation of Wnt/β-catenin signaling in LAD cells.ResultsLncRNA CBR3-AS1 is highly-expressed in LAD and cell lines. LncRNA CBR3-AS1 shows physical association with β-catenin. CBR3-AS1 could facilitate Wnt/β-catenin signaling activation thought promoting nuclear localization of β-catenin. CBR3-AS1 promotes LAD cell proliferation, migration and invasion by targeting Wnt/β-catenin signaling.ConclusionIt can be found that a new functional lncRNA CBR3-AS1 could promote nuclear localization of β-catenin so as to facilitate Wnt/β-catenin signaling activation and regulate the proliferation, migration and invasion of LAD cells.

Dataset Information

LncRNA GASAL1 Interacts with SRSF1 to Regulate Trophoblast Cell Proliferation, Invasion, and Apoptosis Via the mTOR Signaling Pathway.

Publications

LncRNA GASAL1 Interacts with SRSF1 to Regulate Trophoblast Cell Proliferation, Invasion, and Apoptosis Via the mTOR Signaling Pathway.

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