Long non-coding RNA RP4-694A7.2 Promotes Hepatocellular Carcinoma Cell Proliferation and Metastasis through the Regulation of PSAT1

Abstract

Background: Long noncoding RNAs (lncRNAs) have emerged as gene regulators in various cancers, including hepatocellular carcinoma (HCC). However, the biological roles and mechanisms of many lncRNAs in HCC tumorigenesis remain unknown. Aim: To identify novel lncRNAs associated with proliferation and metastasis in HCC. Methods: Expression profiles of lncRNAs were analyzed in HCC using two GSE datasets (GSE94660 and GSE104310). Functional studies were performed, including cell proliferation, colony formation, wound healing, and Transwell assays. Fluorescence in-situ hybridization (FISH), tandem mass tag (TMT) analyses, parallel reaction monitoring (PRM), and rescue assays were performed to evaluate the mechanisms underlying the effects of RP4-694A7.2. Results: RP4-694A7.2 levels were higher in HCC tissues than in normal liver tissues in published GSE datasets and were elevated in HCC cell lines. Cell function assays revealed that RP4-694A7.2 promotes cell proliferation, invasion, and migration. Furthermore, RP4-694A7.2 was primarily found to be located in the cytoplasm by FISH assay. Then, TMT assay was performed to predict proteins associated with RP4-694A7.2, and 28 cytoplastic proteins were identified by PRM. Finally, phosphoserine aminotransferase 1 (PSAT1) was found to be regulated by RP4-694A7.2 to modulate growth and metastasis in HCC cells using a rescue assay. Conclusions: These results suggested that RP4-694A7.2 promotes HCC cell proliferation and metastasis via PSAT1, providing a candidate therapeutic target for further research.

PSAT1 mediated EMT of colorectal cancer cells by regulating Pl3K/AKT signaling pathway

“…Emerging research has provided compelling evidence of PSAT1's crucial role in the initiation and advancement of distant metastasis in breast cancer 48 . Moreover, in mechanistic studies focusing on the malignant characteristics of hepatocellular carcinoma (HCC) cells, the RP4-694A7.2 lncRNA has been shown to promote cell proliferation and metastasis through its interaction with PSAT1 49 . Notably, ectopic expression of MEG3 has demonstrated the ability to significantly inhibit the proliferation, migration, invasion, and EMT of esophageal squamous cell carcinoma (ESCC) cells by down-regulating PSAT1 expression 50 .…”

Epigenetic reactivation of tumor suppressor genes with CRISPRa technologies as precision therapy for hepatocellular carcinoma

“…Our 12-gene TSG panel comprises: (1) regulators of cell cycle, e.g., CDKN2A [ 13 , 14 ]; (2) metabolic enzymes such as BCO2 [ 37 , 38 ] (a regulator of lycopene metabolism), CPS1 [ 39 ] (a liver-specific, intramitochondrial, rate-limiting enzyme in the urea cycle), PTGR1 [ 40 ] (a bifunctional enzyme that inactivates leukotrienes and prostaglandins), and PSAT1 [ 41 , 42 ] (a phosphoserine aminotransferase); (3) regulators of stemness, such as HHIP [ 43 – 49 ] , which is a suppressor of the Hedgehog signaling pathway involved in embryonic development and tumorigenicity; (4) pro-apoptotic factors including the metallothioneins MT1E [ 50 , 51 ] and MT1M [ 52 – 54 ] , which act as a surveillance systems for carcinogens-caused cellular damage; immune-regulators, such as the transmembrane protein TMEM106A [ 55 , 56 ] (an activator of the MAPK and NF-κB signaling pathways implicated in the pro-inflammatory and anti-tumoral M1-type macrophage polarization); and (5) negative regulators of migration, invasion, angiogenesis, and metastasis, such as the liver specific miR-122-5p [ 57 , 58 ] (a post-transcriptional regulator of genes involved in TNF and Notch signaling pathways), PZP [ 59 – 61 ] (a proteinase inhibitor), and TTC36 [ 62 – 64 ] (a regulator of the Wnt- β -catenin pathway). Thus, while we focused on a limited array of phenotypic assays, the multiplexing approach has great potential to reprogram multiple aspects of HCC pathobiology, which could potentially facilitate a more comprehensive and multi-factorial reprogramming of the HCC phenotype, including the tumor microenvironment.…”

Amino acid metabolism regulated by lncRNAs: the propellant behind cancer metabolic reprogramming

“…LncRNA targeting PSAT1 can be found via GSE datasets (GSE94660 and GSE104310) which downloaded from the GEO. LncRNA RP4-694A7.2 can positively correlate with hepatocellular carcinoma proliferation and migration through binding to PSAT1 and promoting its expression [ 55 ]. LncRNAs also inhibited the expression of PSAT1.…”