RNAi for contactin 2 inhibits proliferation of U87-glioma stem cells by downregulating AICD, EGFR, and HES1

Abstract

Glioblastoma is the most common form of malignant brain tumors and has a poor prognosis. Glioma stem cells (GSCs) are thought to be responsible for the aberrant proliferation and invasion. Targeting the signaling pathways that promote proliferation in GSCs is one of the strategies for glioma treatment. In this study, we found increased expression of contactin 2 (CNTN2) and amyloid β precursor protein (APP) in U87-derived GSCs (U87-GSCs). RNA interference (RNAi) for CNTN2 downregulated the expression of APP intracellular domain (AICD), which is the proteolytic product of APP. Treatment with CNTN2 RNAi inhibited the proliferation of U87-GSCs. CNTN2 RNAi decreased the expression of epidermal growth factor receptor and HES1, which are potential targets of AICD. In summary, inhibition of the CNTN2/APP signaling pathway may repress the proliferation in U87-GSCs via downregulating the expression of HES1 and epidermal growth factor receptor. CNTN2/APP/AICD signaling pathway plays an important role in U87 glial tumorigenesis. Further studies are warranted to elucidate the role of these signaling pathways in other sources of GSCs. Depending on their role in proliferation in other sources of GSCs, members of the CNTN2/APP/AICD signaling pathway may provide novel targets for the development of therapy for glioblastomas.

Keywords:

• contactin 2
• CNTN2
• transient axonal glycoprotein-1
• TAG1
• glioma stem cells

Supplementary material

Figure S1 CNTN2 RNAi selection.

Notes: (A) The Western blot shows that CNTN2 RNAi-2 was the most effective among the four RNAi vectors to inhibit CNTN2 expression in U87-GSCs. (B) Gene sequencing results of CNTN2 RNAi-2 after lentiviral infection of U87-GSCs.

Abbreviations: CNTN2, contactin 2; RNAi, RNA interference; U87-GSCs, U87-derived glioma stem cells; GAPDH, glyceraldehyde 3-phosphate dehydrogenase.

Acknowledgments

Yang Guo and Peidong Zhang are co-first authors.

Disclosure

The authors report no conflicts of interest in this work.