<p>LINC00958-MYC positive feedback loop modulates resistance of head and neck squamous cell carcinoma cells to chemo- and radiotherapy in vitro</p>

Abstract

Background Aberrant long non-coding RNA (lncRNA) expression contributes cancer development and resistance to therapy. This study first assessed expression of lncRNA LINC00958 in a variety of human cancers using GEPIA database data and then associated it with prognosis of head and neck squamous cell carcinoma (HNSCC) and investigated LINC00958 interaction with c-Myc and the c-Myc-related gene interplay in HNSCC cells. Materials and methods A cohort of 48 HNSCC vs normal tissues was collected for qRT-PCR analysis of LINC00958 and c-Myc expression and statistical analyses. HNSCC cell lines were subjected to transfection with LINC00958 and c-Myc siRNAs or cDNA and their negative control siRNA or empty vector for qRT-PCR, Western blot, cell viability, colony formation, luciferase reporter, chromatin immunoprecipitation, and RNA immunoprecipitation assays. Results The data showed that LINC00958 expression was upregulated in HNSCC tissues and cell lines, upregulation of which was associated with poor tumor differentiation, advanced tumor stage, and shorter overall survival of patients. In vitro, LINC00958 expression induced HNSCC cell viability and colony formation, whereas knockdown of LINC00958 expression enhanced HNSCC cell sensitivity to ionizing radiation and cisplatin treatment. Mechanistically, LINC00958 is a direct target of c-Myc and can enhance the transcriptional activity of c-Myc, thus to form a positive feedback gene network in HNSCC cells, and in turn to modulate HNSCC cell resistance to chemo- and radiotherapy. Conclusion This study demonstrated the LINC00958 interplay with c-Myc as a feedback loop facilitated HNSCC development and resistance to chemo- and radiotherapy. Targeting of such a network could be further evaluated as a novel therapeutic strategy for HNSCC patients.

SP1 induced long non-coding RNA LINC00958 overexpression facilitate cell proliferation, migration and invasion in lung adenocarcinoma via mediating miR-625-5p/CPSF7 axis

“…The inhibitory effects of LINC00958 knockdown on LAD cells proliferation, migration and invasion revealed the oncogenic properties of LINC00958 in LAD. This observation showed similarity to the reports of enriched present research on the oncogenic nature of LINC00958 in pancreatic cancer, gastric cancer (GC) and cervical cancer [26][27][28].…”

LINC01224/ZNF91 Promote Stem Cell-Like Properties and Drive Radioresistance in Non-Small Cell Lung Cancer

“…[11][12][13] Moreover, it has been found that the expressions of lncRNAs are abnormal during radiotherapy, suggesting that lncRNAs play important roles in the regulation of radioresistance. [14][15][16] In the present study, we found that the expression of LINC01224 increased in irradiation-resistant H1975/IR cells compared with irradiation-sensitive H1975 cells. LINC01224 was transcribed from the enhancer region of ZNF91 and regulated the transcription of ZNF91 by mediating chromatin looping between the ZNF91 enhancer and promoter.…”

Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

“…Moreover, they also explore dysregulated ncRNAs expression through comparing radiotherapy-resistant, radiotherapy-sensitive, and normal cancer tissues or cells, so as to discover key ncRNAs that could regulate radiotherapy sensitivity. We summarized the differently expressed ncRNAs in radiotherapy-resistant, radiotherapy-sensitive, and normal cancer tissues or cells as shown in Table 1 ( Qu et al, 2012 , 2015a , b ; Li et al, 2013 ; Li B. Y. et al, 2017 ; Li L. N. et al, 2017 ; Li et al, 2020 ; Shiiba et al, 2013 ; Zhang et al, 2013 ; Wang et al, 2014 , 2016 , Wang Z. et al, 2019 ; de Jong et al, 2015 ; Lin et al, 2015 ; Maia et al, 2015 ; Suh et al, 2015 ; Sun et al, 2015 ; Xu et al, 2015 ; Zhao et al, 2015 ; Huang et al, 2016 , 2018 , 2019 ; Kang et al, 2016 ; Weng et al, 2016 ; Wu et al, 2016 , 2018 ; Gao et al, 2017a , b ; Han et al, 2017 ; Hu et al, 2017 ; Chen H. et al, 2018 ; Chen et al, 2019 ; Feng et al, 2018 ; He et al, 2018 ; Yang et al, 2018 ; Kong et al, 2019 ; Tian et al, 2019 ; Vahabi et al, 2019 ; Yi et al, 2019 ; Gou et al, 2020 ; Kangboonruang et al, 2020 ; Shuai and Huang, 2020 ).…”