miR-1297 sensitizes glioma cells to temozolomide (TMZ) treatment through targeting adrenomedullin (ADM)

Abstract

Background Gliomas account for about 80% of all malignant brain and other central nervous system (CNS) tumors. Temozolomide (TMZ) resistance represents a major treatment hurdle. Adrenomedullin (ADM) has been reported to induce glioblastoma cell growth. Methods Cell viability was measured using the CCK-8 assay. The apoptosis analysis was performed using the Annexin V-FITC Apoptosis Detection Kit. The mitochondrial membrane potential was determined by JC-1 staining. A nude mouse tumor assay was used to detect tumor formation. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. Activation of Akt and Erk and expression of apoptosis-related proteins were determined by immunoblotting. Results ADM expression has been found upregulated in TMZ -resistant glioma samples based on bioinformatics and experimental analyses. Knocking down ADM in glioma cells enhanced the suppressive effects of TMZ on glioma cell viability, promotive effects on cell apoptosis, and inhibitory effects on mitochondrial membrane potential. Moreover, ADM knockdown also enhanced TMZ effects on Bax/Bcl-2, Akt phosphorylation, and Erk1/2 phosphorylation. Bioinformatics and experimental investigation indicated that miR-1297 directly targeted ADM and inhibited ADM expression. miR-1297 overexpression exerted similar effects to ADM knockdown on TMZ-treated glioma cells. More importantly, under TMZ treatment, inhibition of miR-1297 attenuated TMZ treatment on glioma cells; ADM knockdown partially attenuated the effects of miR-1297 inhibition on TMZ-treated glioma cells. Conclusions miR-1297 sensitizes glioma cells to TMZ treatment through targeting ADM. The Bax/Bcl-2, Akt, and Erk1/2 signaling pathways, as well as mitochondrial functions might be involved.

Identification and validation of a glycolysis‐related taxonomy for improving outcomes in glioma

“…Its presence has been linked to tumor cell proliferation and angiogenesis. [38][39][40][41] Furthermore, ADM mRNA expression levels in brain tumors are positively correlated with tumor grade. 42 Our research findings indicate that the suppression of ADM expression leads to a decrease in glycolysis, migration, invasion, and proliferation of glioma cells.…”

UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway

“…GBM is the most aggressive primary brain tumor in adults and accounts for more than 50% of all gliomas. 25 Although the treatment of GBM has evolved over the years, most patients with GBM still have a very poor prognosis, with a 5-year relative survival rate of 5%. 26 TMZ is a common clinical chemotherapy for GBM, which can cross the blood–brain barrier and trigger tumor cell apoptosis; 27 however, resistance to TMZ develops quickly and frequently.…”

Peptidergic Systems and Cancer: Focus on Tachykinin and Calcitonin/Calcitonin Gene-Related Peptide Families

“…AM expression was upregulated in temozolomide (TMZ)-resistant glioma samples [ 221 ]. miR-1297 targeted AM, blocked its expression, and sensitized glioma cells to TMZ treatment; this could be mediated by the Bax/Bcl-2, Akt, and extracellular signal-regulated protein kinase (ERK)1/2 signaling pathways [ 221 ].…”

“…For this reason, it is crucial to know which receptors are expressed in cancer cells to develop specific antitumor strategies. After targeting AM, an important antitumor strategy has been demonstrated in glioma: miR-1297 blocked its expression and sensitized glioma cells to temozolomide treatment [ 221 ]. The aforementioned is an important finding and research field that must be developed in other tumors.…”