Carboxypeptidase A4 accumulation is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer
INTERNATIONAL JOURNAL OF ONCOLOGY
Authors: Handa, Tadashi; Katayama, Ayaka; Yokobori, Takehiko; Yamane, Arito; Fujii, Takaaki; Obayashi, Sayaka; Kurozumi, Sasagu; Kawabata-Iwakawa, Reika; Gombodorj, Navchaa; Nishiyama, Masahiko; Asao, Takayuki; Shirabe, Ken; Kuwano, Hiroyuki; Oyama, Tetsunari
Abstract
Using whole transcriptome analysis and a lentiviral short hairpin RNA screening library, carboxypeptidase A4 (CPA4) was identified as a novel marker in breast cancer and a therapeutic target in triple-negative breast cancer (TNBC) in the present study. Immunohistochemistry was used to evaluate the presence of CPA4, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki67, epidermal growth factor receptor, cytokeratin 5/6, aldehyde dehydrogenase 1, cluster of differentiation (CD)44, CD24, claudins, E-cadherin, vimentin and androgen receptor in 221 cases of breast cancer, including 68 TNBC cases. The effects of CPA4 on the viability and migration ability of TNBC cells were analyzed using RNA interference methods. Increased CPA4 expression, specifically in the cytoplasm of cancer tissue cells, was detected. Furthermore, high CPA4 expression in TNBC cases was associated with low expression of E-cadherin and with the expression of cancer stem cell markers (high CD44/low CD24). Patients with TNBC and high levels of CPA4 expression had a significantly poorer prognosis compared with those with low CPA4 expression. Notably, viability and migration were reduced, but E-cadherin expression was upregulated in CPA4-suppressed TNBC cells. The present data suggested that CPA4 may be a novel inducer for epithelial-mesenchymal transition, which is characterized by the downregulation of E-cadherin and mesenchymal phenotypes. To conclude, CPA4 may be a marker for poor prognosis and a promising therapeutic target in TNBC with aggressive phenotypes.
circCPA4 acts as a prognostic factor and regulates the proliferation and metastasis of glioma
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Authors: Peng, Hao; Qin, Chaoying; Zhang, Chao; Su, Jun; Xiao, Qun; Xiao, Yao; Xiao, Kai; Liu, Qing
Abstract
Circular RNAs (circRNAs) are reported to play vital roles in tumour process and might be potential prognostic biomarkers and therapeutic targets for tumours. But the expression and function of circRNAs in glioma remain unclear. Here, we performed circRNA microarray analysis of glioma tissues and matched normal brain tissue samples to explore the circRNA profile in glioma. GO analysis, KEGG and Reactom pathway analysis of linear mRNA transcripts corresponding to circRNAs were performed to study the involved biological process and pathways. The clinical significance of the selected circRNA was investigated by Kaplan-Meier survival analysis. Relevant biological function, such as cell proliferation and metastasis, was detected in vitro and in vivo. And possible mechanism of the regulatory function of the selected circRNA in glioma was explored. We found that circCPA4 (hsa_circ_0082374) up-regulated the most in glioma tissues and high levels of circCPA4 were positively related to poor outcome of glioma. And knockdown of circCPA4 suppresses cell proliferation and metastasis in glioma. Moreover, circCPA4 interacts with let-7 and serves as a sponge for let-7. Through the competitive endogenous RNA (ceRNA) mechanism, circCPA4 sponges let-7 to regulate the expression of CPA4 and glioma progression. The circCPA4/let-7/CPA4 axis regulates glioma progression by ceRNA mechanism, and circCPA4 could be a novel prognostic biomarker and target for glioma treatment.