Analysis of 20 genes at chromosome band 12q13: RACGAP1 and MCRS1 overexpression in nonsmall‐cell lung cancer

Abstract

Chromosomal aberrations at 12q13 are frequent in nonsmall-cell lung cancer (NSCLC). Here, we examined mRNA expression of 20 genes within chromosome band 12q13 by quantitative real-time polymerase chain reaction in NSCLC. Of the 20 genes, nine were upregulated, while two genes were downregulated. Among the nine upregulated genes, mRNA values of RACGAP1, MCRS1, EIF4B, WNT1, and PTGES3 were significantly higher in NSCLCs compared with normal lung tissues. Subsequently, overexpressions of RACGAP1 and MCRS1 were confirmed at the protein level in tissues and cultured cells of lung cancer by immunostaining and Western blot. RACGAP1 was labeled in the nucleus of tumor cells in 89% of the tumor specimens. In the cultured cells, RACGAP1 was present principally in the nucleus of nonmitotic cells, but showed a diffuse distribution in the cytoplasm of mitotic cells (metaphase) and at the contractile ring between two separating daughter cells (telophase). Furthermore, RACGAP1 downregulation by RNA interference caused cytokinesis defects, indicating that RACGAP1 is required for cytokinesis. MCRS1 was stained in all tumor specimens and strongly stained in 31% of cases. Interestingly, MCRS1 exhibits different localization in the mitotic cells of cultured immortalized human bronchial epithelial cells and cultured lung cancer cells. In vitro, downregulation of MCRS1 in lung cancer cells inhibited cell proliferation, increased apoptosis, and induced cell cycle arrest at the G1 phase. These findings indicate that RACGAP1 and MCRS1 may be cancer-related genes in NSCLC.

Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

“…Little is known about the biological function of Racgap1 in B-lymphoma, but its value as biomarker for early recurrence and heightened aggressiveness of solid cancers is increasingly being recognized [25,26,27]. Racgap1 , a positive regulator of Rac activity, has been reported to play an important role in cytokinesis [28], differentiation of myeloid cells [29] and, interestingly, increased production of reactive oxygen species (ROS) [30].…”

RacGAP1 Is a Novel Downstream Effector of E2F7-Dependent Resistance to Doxorubicin and Is Prognostic for Overall Survival in Squamous Cell Carcinoma

“…This is also the first report to show that overexpression of tumor-associated RacGAP1 is directly controlled by E2F7, which itself is known to be overexpressed in SCC and to induce drug resistance (15). Overexpression of RacGAP1 has been reported in high-grade meningiomas, non-small cell lung cancer, gastric cancer, hepatocellular carcinoma, breast cancer (24,38,(42)(43)(44) as well as in the more aggressive tumor phenotypes of epithelial ovarian cancer, highgrade breast cancer, and invasive cervical cancer (45)(46)(47). However, it is unknown whether the overexpression of RacGAP1 in these tumors is linked to overexpression of E2F7.…”

New Insight into microRNA Functions in Cancer: Oncogene–microRNA–Tumor Suppressor Gene Network

“…In early studies, we screened novel cancer-related genes and found that microspherule protein 1 (MCRS1) was overexpressed in lung cancer (Liang et al, 2013). Subsequently, we confirmed the overexpression of MCRS1 was associated with the cellular proliferation, EMT, and metastasis (Liu et al, 2014).…”