XB130, a New Adaptor Protein, Regulates Expression of Tumor Suppressive MicroRNAs in Cancer Cells

Abstract

XB130, a novel adaptor protein, promotes cell growth by controlling expression of many related genes. MicroRNAs (miRNAs), which are frequently mis-expressed in cancer cells, regulate expression of targeted genes. In this present study, we aimed to explore the oncogenic mechanism of XB130 through miRNAs regulation. We analyzed miRNA expression in XB130 short hairpin RNA (shRNA) stably transfected WRO thyroid cancer cells by a miRNA array assay, and 16 miRNAs were up-regulated and 22 miRNAs were down-regulated significantly in these cells, in comparison with non-transfected or negative control shRNA transfected cells. We chose three of the up-regulated miRNAs (miR-33a, miR-149 and miR-193a-3p) and validated them by real-time qRT-PCR. Ectopic overexpression of XB130 suppressed these 3 miRNAs in MRO cells, a cell line with very low expression of XB130. Furthermore, we transfected miR mimics of these 3 miRNAs into WRO cells. They negatively regulated expression of oncogenes (miR-33a: MYC, miR-149: FOSL1, miR-193a-3p: SLC7A5), by targeting their 3′ untranslated region, and reduced cell growth. Our results suggest that XB130 could promote growth of cancer cells by regulating expression of tumor suppressive miRNAs and their targeted genes.

Role of miR-193a in Cancer: Complexity and Factors Control the Pattern of its Expression

“…Based on their study, Takeshita and his colleagues validated the upregulation miR-193a-3p in XB130 knockdown thyroid cancer cells [72]. In addition, overexpression of miR-193a-3p significantly induced both early and late apoptosis in XB130 knockdown thyroid cancer cells [72]. Furthermore, the expression of pri-miR-193a-3P was also increased in XB130 knockdown cells [72].…”

“…XB130 has been reported as a potent regulator of several miRNAs including miR-193a-3p [72]. Based on their study, Takeshita and his colleagues validated the upregulation miR-193a-3p in XB130 knockdown thyroid cancer cells [72]. In addition, overexpression of miR-193a-3p significantly induced both early and late apoptosis in XB130 knockdown thyroid cancer cells [72].…”

“…XB130 (also known as actin filament associated protein 1-like2, AFAPIL2) is a member of adaptor proteins which are involved in intracellular signal transductions and cellular motility [71]. XB130 has been reported as a potent regulator of several miRNAs including miR-193a-3p [72]. Based on their study, Takeshita and his colleagues validated the upregulation miR-193a-3p in XB130 knockdown thyroid cancer cells [72].…”

XB130: A novel adaptor protein in cancer signal transduction

“…Microarray analysis identified that 246 genes were significantly changed in XB130 small hairpin RNA (shRNA)-transfected cells, among which 57 genes were involved in cell proliferation and survival, as well as transcriptional regulation. To further explore the mechanisms that XB130 regulates gene expression associated with cell proliferation or survival, Takeshita et al (50) analyzed miRNA expression in XB130 knockdown WRO cells, based on the estimation that ~30% of all human genes can be regulated by miRNAs (51). They speculated that XB130 may regulate growth-related expression of miRNAs and in this way control the genes associated with cell proliferation or survival.…”

AFAP1L2 (actin filament associated protein 1-like 2)

“…XB130 is aberrantly expressed in human cancers and has been shown to control tumour growth in vivo . XB130 regulates thyroid cancer cell proliferation by controlling microRNA miR-33a, 149a and 193a expression to alter oncogenes Myc, FosL1, and SCL7A5 protein levels (Takeshita et al, 2013).…”