HNRNPA2B1 Affects the Prognosis of Esophageal Cancer by Regulating the miR-17-92 Cluster

Abstract

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes. Accumulating evidence suggests that dysregulation of m6A modification significantly correlates with tumorigenesis and progression. In this study, we observed an increased expression and positive correlations of all 25 m6A regulators in esophageal cancer (ESCA) data obtained from the TCGA database. Through expression profiling of these regulators, a prognostic score model containing HNRNPA2B1, ALKBH5, and HNRNPG was established, and the high-risk subgroup exhibited strong positive correlations with ESCA progression and outcome. The risk score obtained from this model may represent an independent predictor of ESCA prognosis. Notably, the gene most frequently associated with increased risk was HNRNPA2B1; in ESCA, the increased expression of this gene alone predicted poor prognosis by affecting tumor-promoting signaling pathways through miR-17-92 cluster. An experimental study demonstrated that elevated HNRNPA2B1 expression was positively associated with distant metastasis and lymph node stage, and predicted the poor outcomes of ESCA patients. Knockdown of HNRNPA2B1 significantly decreased the expression of miR-17, miR-18a, miR-20a, miR-93, and miR-106b and inhibited the proliferation of ESCA cells. Therefore, our study indicated that the dynamic changes in 25 m6A regulators were associated with the clinical features and prognosis of patients with ESCA. Importantly, HNRNPA2B1 alone may affect the prognosis of patients with ESCA by regulating the miR-17-92 cluster.

RNA m6A Methylation Regulators Multi-Omics Analysis in Prostate Cancer

“…Still other studies have found that HNRNPA2B1 can promote cell proliferation and regulate apoptosis of human colon cancer via the ERK/MAPK signaling, which indicates HNRNPA2B1 provides a potential treatment site for colon cancer (Tang et al, 2021). At the same time, also studies have found that HNRNPA2B1 was the oncogenic gene in esophageal cancer(ESCA), the increased expression of HNRNPA2B1 could predict adverse prognosis of ESCA by affecting tumor-promoting signaling pathways, silencing HNRNPA2B1 could inhibit the proliferation of ESCA cells (Li et al, 2021). Also overexpression of HNRNPA2B1 is correlated with poor survival in gastric cancer (GC), multiple myeloma (MM) and ovarian cancer and HNRNPA2B1 acts as an oncogenic role in their progression (Yang et al, 2020;Jiang et al, 2021;Peng et al, 2021).…”

Role of m6A writers, erasers and readers in cancer

“…HNRNPC enhances the stability of ZEB1 and ZEB2 mRNA and promotes the development of esophageal squamous cell carcinoma [ 266 ]. High expression of HNRNPA2B1 has been associated with a low survival rate in esophageal cancer [ 267 ].…”

Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets

“…HnRNPA2/B1 could serve as a trigger for RNA switch to modulate the function of miRNAs or lncRNAs in cancer cells [ 90 ]. Illustratively, hnRNPA2/B1 affected the prognosis of ESCA by regulating the miR-17-92 cluster [ 91 ], facilitated the malignant phenotype of OC by activating Lin28B [ 92 ], and advanced lung cancer progression by contributing to miR-106b-5p maturation [ 88 ]. In some cases, the oncogenic roles and expression of hnRNPA2/B1 were instead impacted by certain upstream effectors.…”