LncRNA miR205HG hinders HNRNPA0 translation: anti‐oncogenic effects in esophageal carcinoma

Abstract

Esophageal carcinoma (ESCA) affects 4 450 000 people and causes approximately 400 000 deaths annually worldwide, making it the sixth most lethal and eighth most common cancer. Patients with ESCA are often diagnosed at the later stages in which cancer cell metastasis is the main factor contributing to the low 5‐year survival rate (< 20%) of this disease. Long noncoding RNAs (lncRNAs) are a group of regulatory RNAs with a length of > 200 nucleotides but which fail to encode proteins. In this study, by using real‐time quantitative PCR, we found that the expression of the miR205 host gene (miR205HG; a lncRNA) was downregulated in ESCA tumors when compared with normal esophageal tissues or adjacent normal tissues of tumors. Furthermore, we demonstrated that miR205HG modulates the expression of extracellular matrix‐related genes in ESCA cells. In the transwell assay, downregulation of miR205HG contributes to migration and invasion of ESCA cells. In relation to the mechanism, our data show that miR205HG interacts with heterogeneous nuclear ribonucleoprotein A0 (HNRNPA0) mRNA and then hamper its translation by interacting with lin‐28 homolog A (LIN28A). Altogether, we highlight that the miR205HG‐HNRNPA0 axis is implicated in the migration and invasion of ESCA cells and that these members of this pathway may serve as therapeutic targets to inhibit metastasis of ESCA.

MIR205HG/LEADR Long Noncoding RNA Binds to Primed Proximal Regulatory Regions in Prostate Basal Cells Through a Triplex- and Alu-Mediated Mechanism

“…Our previous work demonstrated, for the first time, the pivotal role of the chromatin-associated lncRNA MIR205HG/LEADR in controlling the basal phenotype of prostate epithelial cells (Profumo et al, 2019). Understanding the mechanism of action of MIR205HG/LEADR will allow to dissect the processes governing differentiation of epithelial cells, which often appear deregulated in cancer (Ferrari and Gandellini, 2020), and eventually lay the foundations for the development of novel therapeutic approaches for tumors where MIR205HG/ LEADR expression is deregulated (Di Agostino et al, 2018;Li et al, 2019;Liu et al, 2020;Song et al, 2021;Dong et al, 2022).…”

“…An oncogenic role has been proposed for MIR205HG in several cancers characterized by the expansion of basal cells, such as cervical (Li et al, 2019), lung squamous cell (Liu et al, 2020), head and neck squamous cell carcinomas (Di Agostino et al, 2018). A tumor-suppressive function has been instead reported in esophageal adenocarcinoma, where MIR205HG is downregulated (Song et al, 2021;Dong et al, 2022). From the mechanistic side, most of the studies suggest that MIR205HG would act post-transcriptionally as sponge for various miRNAs, among which miR-122-5p, miR-299-3p (Guo et al, 2021) and miR-590-3p, or by hindering the translation of HNRNPA0 mRNA (Dong et al, 2022).…”

“…A tumor-suppressive function has been instead reported in esophageal adenocarcinoma, where MIR205HG is downregulated (Song et al, 2021;Dong et al, 2022). From the mechanistic side, most of the studies suggest that MIR205HG would act post-transcriptionally as sponge for various miRNAs, among which miR-122-5p, miR-299-3p (Guo et al, 2021) and miR-590-3p, or by hindering the translation of HNRNPA0 mRNA (Dong et al, 2022). However, data from the lncAtlas (Mas-Ponte et al, 2017) (Supplementary Figure S1) and from our group (Profumo et al, 2019) indicate that the expression of MIR205HG is prevalently nuclear and chromatin-associated.…”

The metabolism-related lncRNA signature predicts the prognosis of breast cancer patients

“…Among the identified lncRNAs, MIR205HG, USP30-AS1, MIR200CHG, and TFAP2A-AS1 were associated with tumor progression, each mediating different processes of tumor development. LncRNA miR205HG interacts with HNRNPA0 mRNA and then inhibits the migration and invasion of esophageal carcinoma cells 31 . Repression of mitophagy by USP30-AS1 may have a role in the development of glioma tumors 32 .…”

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

“…But unlike p53, hnRNPA0 repaired DNA damage caused by chemotherapy and drove cisplatin resistance by the post-transcriptional stabilization of p27(Kip1) and Gadd45α mRNAs [ 29 , 30 ]. However, the translation process and oncogenic effects of hnRNPA0 could be hindered by lncRNA miR205HG in esophageal carcinoma (ESCA), in which hnRNPA0 was highly expressed [ 31 ].…”