The function and mechanism of the JARID2/CCND1 axis in modulating glioma cell growth and sensitivity to temozolomide (TMZ)

ABSTRACT

A maximal surgical resection followed by radiotherapy and chemotherapy with temozolomide (TMZ) as the representative agent is the standard therapy for gliomas. However, tumor cell resistance to radiotherapy and chemotherapy leads to poor prognosis and high mortality in patients with glioma. In the present study, we demonstrated that JARID2 was downregulated and CCND1 was upregulated within glioma tissues of different grades and glioma cells. In tissue samples, JARID2 was negatively correlated with CCND1. JARID2 overexpression significantly inhibited glioma cell viability, promoted glioma cell apoptosis upon TMZ treatment, and increased p21, cleaved-PARP, and cleaved-caspase3 in TMZ-treated glioma cells. JASPAR tool predicted the possible binding sites between JARID2 and CCND1 promoter regions; through direct binding to CCND1 promoter region, JARID2 negatively regulated CCND1 expression. Under TMZ treatment, JARID2 overexpression inhibited CCND1 expression, promoted glioma cell apoptosis, and increased p21, cleaved-PARP, and cleaved-caspase3 in glioma cells treated with TMZ; meanwhile, CCND1 overexpression exerted opposite effects on glioma cells treated with TMZ and partially reversed the effects of JARID2 overexpression. In conclusion, JARID2 targets and inhibits CCND1. The JARID2/CCND1 axis modulates glioma cell growth and glioma cell sensitivity to TMZ.

KEYWORDS:

• Gliomas
• Temozolomide (TMZ)
• cell growth
• resistance
• JARID2
• CCND1

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethical approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of Xiangya Hospital (approval no. 201803393) and with the 1964 Helsinki Declaration. Informed consent to participate in the study has been obtained from participants.

Consent for publication

Consent for publication was obtained from the participants.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This study was supported by National Natural Science Foundation of China (NO. 81803582), the Hunan Provincial Natural Science Foundation of China (NO.2020JJ4896);<#funding-source;>Natural Science Foundation of Hunan Province</#funding-source;> [<#award-id;>2020JJ4896</#award-id;>];