Altered Expression Patterns of Heterogeneous Nuclear Ribonucleoproteins A2 and B1 in the Adrenal Cortex

Abstract

S U M M A R YSeveral proteins implicated in hormonogenesis of the adrenal cortex have alternatively spliced isoforms, which respond differently to adrenocorticotropic hormone (ACTH). Heterogeneous nuclear ribonucleoproteins A2 and B1 are among the abundant pre-mRNA-binding proteins involved in alternative splicing. We examined the expression of A2 and B1 in normal adrenal cortex and tumors. B1 was variably expressed in the zona fasciculata-reticularis, although A2 was diffusely expressed in the three zones. B1 was more abundant in compact cells than clear cells, and B1 expression was frequent in the zona reticularis, which consists mainly of compact cells. In three kinds of cortical adenomas autonomously producing hormones, B1 was generally overexpressed and there were no significant differences among them. In cortisol-producing tumors, non-tumor parts of the cortex, which were generally atrophic due to low ACTH, had less B1 protein than normal adrenals. These results suggested a correlation between B1 expression and the hormonal activity responding to ACTH. In vitro ACTH stimulation induced a biphasic expression of B1 in an H295R cortical carcinoma cell line, and it paralleled hormonogenesis. Conclusively, B1 expression varied in relation to the hormonal activity responding to the ACTH, and it may provide a key to elucidating the splicing mechanisms involved in hormonogenesis.

Global Profiles of Gene Expression Induced by Adrenocorticotropin in Y1 Mouse Adrenal Cells

“…Alternative splicing can influence protein function, protein-protein interactions, cell proliferation and other aspects of cell regulation independent of gene expression (39). Although effects of ACTH on alternative splicing have not been demonstrated directly, recent findings that ACTH down-regulates hnrpb1 (one of the pre-mRNA binding proteins involved in alternative splicing) at the protein level in adrenocortical cells (40) lends additional support to this hypothesis.…”

The roles of hnRNP A2/B1 in RNA biology and disease

“…Reducing hnRNPA2/B1 can inhibit the proliferation of cervical cancer cells and increase their sensitivity to irinotican combined with loplatin chemotherapy (Shi et al, 2018). In addition, hnRNPA2/B1 is involved in the development of nasopharyngeal (Zhang & Li, 2019), esophageal (Zhang & Li, 2019), prostate (Yang et al, 2018), colon (Wu et al, 2019), kidney (Wu et al, 2005), ovarian (Lee et al, 2010), and cervical cancers (Orru, Cunniffe, Ryan, & Schwartz, 2012) and melanoma (Suzuki et al, 2010).…”