m6A-Mediated Upregulation of LINC00857 Promotes Pancreatic Cancer Tumorigenesis by Regulating the miR-150-5p/E2F3 Axis

Abstract

The mortality and morbidity rates of pancreatic cancer (PC) have been increasing over the past two decades. Recent evidence indicates that long non-coding RNAs (lncRNAs) are usually dysregulated in the tumorigenesis and progression of PC. In the present study, we showed that the expression of LINC00857 was upregulated in PC and associated with poor prognosis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database and validated in our PC tissues and cell lines. N6-Methyladenosine (m6A) was highly enriched within LINC00857 and enhanced its RNA stability. Knockdown of LINC00857 remarkably inhibited the proliferation and promoted the apoptosis of PC cells. Then, by using bioinformation analysis and verified experiments, we identified that LINC00857 functioned as a competing endogenous RNA (ceRNA) for sponging miR-150-5p, leading to the upregulation of its target E2F3 in PC cells. Taken above, our study revealed a potential ceRNA regulatory pathway in which LINC00857 modulates E2F3 expression by binding to miR-150-5p, ultimately promoting tumorigenesis in PC. LINC00857/miR-150-5p/E2F3 regulatory axis may be taken as an alternative therapeutic target for treating PC.

The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

“…The wild-type TP53 gene, namely tumor suppressor gene, has a control and negative regulation effect on cell proliferation. However, the mutant TP53 gene lost its tumor suppressor effect and promoted the transformation of cells to malignancy ( Duffy et al, 2020 ; Zhu et al, 2020 ; Meng X. et al, 2021 ). Our results showed that TP53 mutant patients in the high-risk subgroup had the worst prognosis, and TP53 wild-type patients in the low-risk subgroup had the best prognosis, which also indicated that higher mutation rate of TP53 was associated with poorer prognosis.…”

N6-Methylandenosine-Related lncRNAs Predict Prognosis and Immunotherapy Response in Bladder Cancer

“…Likewise, lncRNA LNMAT1 was shown to promote bladder cancer lymphatic metastasis via upregulation of CCL2 and recruitment of macrophages into tumors ( 18 ). Recently, some studies have suggested an indispensable role of m6A modifications in the dysregulation of lncRNAs during tumorigenesis ( 20 , 21 ). However, the role and the mechanisms underlying m6A modification in the dysregulation of lncRNAs in bladder cancer remain unknown.…”

N6-Methyladenosine-Related lncRNA Signature Predicts the Overall Survival of Colorectal Cancer Patients

“…Accumulating evidence indicates that the m6A modifications of lncRNA may affect the development and progression of cancers. The m6A regulators reportedly act as a lncRNA structural switch, participates in the lncRNA-mediated competing endogenous RNA model, and enhances the stability of lncRNA to serve its functions, thereby influencing tumor initiation and progression [ 26 , 27 , 28 ]. For example, m6A-induced LNCAROD can promote the development of head and neck squamous cell cancer by forming a ternary complex with YBX1 and HSPA1A [ 26 ].…”