The localization of hnRNP A2/B1 in nuclear matrix and the aberrant expression during the RA‐induced differentiation of human neuroblastoma SK‐N‐SH cells

Abstract

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is involved in the synthesis of RNA. Its expression is up-regulated in many tumor cell lines. In this study, we investigated the distribution of hnRNP A2/B1 in the nuclear matrix, including its co-localization with expression products of related genes. Results from 2-DE PAGE and MS showed that hnRNP A2/B1 is involved with components of nuclear matrix proteins of SK-N-SH cells, and that its expression level is down-regulated after retinoic acid (RA) treatment. Protein immunoblotting results further confirm the existence of hnRNP A2/B1 in the nuclear matrix, as well as its down-regulation after RA treatment. Immunofluorescence microscopy observation showed that hnRNP A2/B1 localized in nuclear matrix of SK-N-SH cells and its distribution regions were altered after RA treatment. Laser scanning confocal microscopy observation showed that hnRNP A2/B1 co-localized with c-Myc, c-Fos, P53, and Rb in SK-N-SH cells. The co-localized region was altered as a result of RA treatment. Our data proved that hnRNP A2/B1 is a nuclear matrix protein and can be up-regulated in human neuroblastoma. The expression and distribution of hnRNP A2/B1 can affect the differentiation of SK-N-SH cells, as well as its co-localization with related oncogenes and tumor suppressor genes.

Heterogeneous Nuclear Ribonucleoprotein A2/B1 Regulates the Self-Renewal and Pluripotency of Human Embryonic Stem Cells Via the Control of the G1/S Transition

“…Thus, hnRNP A2/B1 was required to maintain the undifferentiated and epithelial phenotypes of hESCs. Our findings are also supported by two recent studies in which hnRNP A2/B1 expression was decreased when undifferentiated and epithelial neuroblastoma and gastric adenocarcinoma were induced to differentiate []. However, the previous study reported that hnRNP A2/B1 knockdown is correlated with an increase of E‐cadherin expression and downregulation of E‐cadherin repressor molecules in the mesenchymal type of lung cancer cells .…”

“…Recent studies suggested that p53 may be directly associated with hnRNP A2/B1 in some cancer cell lines [], and other studies also suggested that hnRNP A2 gene itself may be a target of p53, since p53 represses the expression of hnRNP A2 mRNA . However, it seems that hnRNP A2 does not modulate p53 expression directly, because p53 mRNA and protein levels are not significantly altered in hnRNP A2 knockdown cancer cells [].…”

“…For example, hnRNP A2 binds telomeric DNA repeats and the RNA component of telomerase simultaneously, which suggests its role in telomere maintenance . hnRNP A2/B1 is upregulated or mislocalized in human cancers such as lung, brain, colon, breast, pancreatic, and stomach carcinoma []. Furthermore, hnRNP A2/B1 colocalizes with c‐myc, c‐fos, p53, and Rb in undifferentiated neuroblastoma and gastric adenocarcinoma cells [].…”

“…hnRNP A2/B1 is upregulated or mislocalized in human cancers such as lung, brain, colon, breast, pancreatic, and stomach carcinoma []. Furthermore, hnRNP A2/B1 colocalizes with c‐myc, c‐fos, p53, and Rb in undifferentiated neuroblastoma and gastric adenocarcinoma cells []. As hnRNP A2/B1 is implicated in the splicing of many genes , the regulation of alternative splicing by upregulation of hnRNP A2/B1 may contribute to tumor cell proliferation and progression.…”

The aberrant expression and localization of prohibitin during apoptosis of human cholangiocarcinoma Mz‐ChA‐1 cells

“…These studies were performed as previously described [18]. Mz‐ChA‐1 cells and ESC‐3‐treated cells were seeded on a cover slip and cultured overnight.…”