Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p

Abstract

Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance. However, the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance, we induce TMZ-resistant GBM cells, perform a lncRNA microarray of the parental and TMZ-resistant cells, and find an unreported lncRNA in GBM, lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence), correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore, lnc-TALC increased MGMT expression by mediating the acetylation of H3K9, H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients, lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.

Dual functionalized brain-targeting nanoinhibitors restrain temozolomide-resistant glioma via attenuating EGFR and MET signaling pathways

“…Gene expression profiling was performed for the LN229R and the parental cells LN229 and RTK genes had higher expression levels in LN229R cells than in LN229 cells, especially for EGFR and MET ( Supplementary Fig. 2a, Supplementary Data 2), consistent with our and other teams' work 11,33,35 . LN229R exhibited higher levels of EGFR and MET expression and phosphorylation in mouse orthotopic models bearing GBM xenografts ( Supplementary Fig.…”

“…According to our previous work 33,34 , we established TMZresistant GBM cells named LN229R, U87MGR and HG9R through TMZ treatment on LN229, U87MG and patientderived GBM cell HG9 ( Supplementary Fig. 1e).…”

“…However, the survival rates still remain low from inherent TMZ resistance or relapse with chemotherapyresistant gliomas 42,43 . Currently, there are few alternate treatment options for patients with TMZ-resistant gliomas, and adjuvant TMZ chemotherapy options are a popular area of intense research 33 . Clinical practices and experimental evidence have clearly revealed that biologic therapies are effective only in a certain percentage of GBM expressing the appropriate targets 4 .…”

Elevated microRNA‐20b‐3p and reduced thioredoxin‐interacting protein ameliorate diabetic retinopathy progression by suppressing the NLRP3 inflammasomes

“…MicroRNA‐20b‐3p (miR‐20b‐3p) is a member of the miRNAs that has been seldom studied. As reported, the effects of miR‐20b‐3p have been identified in the progression of hyperoxaluria‐induced calcium oxalate deposition and glioblastoma . In addition, thioredoxin‐interacting protein (TXNIP) is a broadly expressed protein involved in cellular redox control and apoptosis, and the TXNIP expression could be stimulated by a high glucose level .…”

NoncoRNA: a database of experimentally supported non-coding RNAs and drug targets in cancer

“…Currently, more and more evidences have been proved that non-coding RNAs play critical roles in drug resistance [3][4][5][6]. ncRNAs including long non-coding RNAs (lncRNAs), microRNAs (miRNAs), circular RNAs (circRNAs), and PIWI-interacting RNAs (piRNAs) are suggested to be the potential promising therapeutic targets for overcoming drug resistance in the treatment of human cancers [7][8][9][10]. Due to their functional importance, ncRNAs are under intense study at present, and some databases have been built to describe ncRNAs' functional characterization, such as ncDR, Lnc2Cancer, SM2miR, CircR2Disease, and piRBase.…”