The role of lncRNA just proximal to XIST (JPX) in human disease phenotypes and RNA methylation: The novel biomarker and therapeutic target potential

Kuang, Yirui; Shen, Wenyue; Zhu, Hecheng; Huang, Hao; Zhou, Quanwei; Yin, Weiqiang; Yi, Zhou; Cao, Yudong; Wang, Lei; Li, Xuewen; Ren, Chao; Jiang, Xingjun

doi:10.1016/j.biopha.2022.113753

Cited by 2 publications

(3 citation statements)

References 68 publications

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“…In addition, the ceRNET perspective has opened a new scenario, wherein even functionally unrelated transcripts can unexpectedly cross talk with each other by competitively binding to a shared microRNA, and new functions have been assigned to molecules involved in distant and unrelated biological processes [13,14]. This is the case of the lncRNA JPX; in recent years, it has been discovered that JPX, beyond serving as an activator of XIST expression essential for X chromosome inactivation, is aberrantly expressed and associated with clinicopathological traits in numerous diseases, particularly cancers, where it acts as an oncogene in the majority of cases (lung cancer, oral squamous cell carcinoma, cervical cancer, osteosarcoma, esophageal squamous cell carcinoma, gastric cancer, ovarian cancer, glioblastoma multiforme, and acute megakaryoblastic leukemia), but also as a tumor suppressor in some others (hepatocellular carcinoma, breast cancer, and uveal melanoma) [36,37]. In lung cancer, JPX was reported to be upregulated in three experiments, where its expression was correlated with clinical characteristics, such as tumor size, stage, and poor survival [16,17,[20][21][22].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies demonstrated that JPX overexpression was able to prompt cancer hallmarks in cell culture [36,37]. We evaluated this ability in our experimental system, as well as the effects of miR-378a boosting, and those of their combination, by performing an array of biological assays, such as the MTT assay for measuring cell proliferation, wound healing assays for cell migration, and the transwell invasion assay for cell invasion.…”

Section: Jpx Promotes Cell Proliferation Migration and Invasion By Sp...mentioning

confidence: 99%

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A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer

Mosca,

Pezzullo,

De Leo

et al. 2024

Cancers

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Lung cancer is the leading cause of cancer-related death worldwide. Non-coding RNAs are emerging as critical players for the onset and progression of cancer. Analyses of three different datasets revealed that the lncRNA JPX was overexpressed in adenocarcinoma tissues in comparison to normal lungs, as expected for an oncogene. Intriguingly, the predicted binding miR-378a-3p showed a significant inverse correlation with JPX expression. The lncRNA/miRNA physical interaction was validated by reporter vectors. Then, the oncogenic activity of JPX, the tumor-suppressive role of miR-378a-3p, and the contribution of their functional interaction to cancer hallmarks were demonstrated using assays for cell proliferation, migration, invasion, and 3D-spheroid formation. Finally, molecular circuits were investigated by boosting the expression of both JPX and miR-378a-3p, singularly and in combination, demonstrating that JPX counteracted miR-378a-3p silencing activity toward its oncogenic targets GLUT1, NRP1, YY1, and Wnt5a. Overall, the data unveil a novel ceRNET (competing endogenous RNA network), wherein JPX acts as a ceRNA by binding to miR-378a-3p, thus reducing the miRNA silencing activity toward its downstream targets, and eliciting oncogenic pathways driving lung cancer. The knowledge of the network may pave the way to develop new diagnostic panels, and innovative RNA-targeted and RNA-based therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Jpx Promotes Cell Proliferation Migration and Invasion By Sp...mentioning

confidence: 99%

A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer

Mosca,

Pezzullo,

De Leo

et al. 2024

Cancers

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“…Recently, increasing evidence supports the importance of lncRNAs in multiple diseases, including in the regulation of hypertrophic scars [ 26 ‒ 28 ]. Here, we presented lncRNA expression profiles from 5 paired HS and matched adjacent normal tissues (NS) through RNA-Seq.…”

Section: Discussionmentioning

confidence: 99%

HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8

Ma,

Liu,

Xia

et al. 2023

ABBS

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Hypertrophic scar (HS) is one of the most common sequelae of patients, especially after burns and trauma. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating HS remain underexplored. Human hypertrophic scar-derived fibroblasts (HSFBs) have been shown to exert more potent promoting effects on extracellular matrix (ECM) accumulation than normal skin-derived fibroblasts (NSFBs) and are associated with enhanced HS formation. The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms. LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA (HSFAS). HSFAS overexpression significantly induces fibroblast proliferation, migration, and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs, while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation, migration, and myofibroblast trans-differentiation of HSFBs. Mechanistically, HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8). ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation, migration, myofibroblast trans-differentiation and apoptosis. Thus, our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function. Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.

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The role of lncRNA just proximal to XIST (JPX) in human disease phenotypes and RNA methylation: The novel biomarker and therapeutic target potential

Cited by 2 publications

References 68 publications

A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer

A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer

HSFAS mediates fibroblast proliferation, migration, trans-differentiation and apoptosis in hypertrophic scars via interacting with ADAMTS8

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