LncRNA ENST869 Targeting Nestin Transcriptional Region to Affect the Pharmacological Effects of Chidamide in Breast Cancer Cells

Abstract

Breast cancer is one of the leading threats to the health of women. It has the highest incidence and mortality in women worldwide. Although progress has been made in the development and application of anti-breast cancer drugs such as Chidamide and others, the occurrence of drug resistance limits the effective application of chemotherapies. The purpose of this study is to explore the role of LncRNA in the pharmacological effect of Chidamide in breast cancer therapy. The human breast cancer MCF-7 or MDA-MB-231 cells were used as the research cell models. The RNA library screening and high-throughput sequencing comparative analysis was conducted. The binding of LncRNA and its downstream target genes in RNA and protein levels was tested. The results showed that the expression of LncRNA ENST869 in cells treated with Chidamide increased significantly, as demonstrated by real-time PCR and cell viability assay. RNAplex analysis showed that LncRNA ENST869 and Nestin mRNA may interact. RNA interference and Western blot analysis indicated that LncRNA ENST869 could target and regulate the expression of Nestin. Luciferase assay and RNA-protein pulldown showed that LncRNA ENST869 affected Nestin transcription. There might be a highly active binding region of LncRNA ENST869 in regulating Nestin transcriptional activity within the site of 250 bp upstream of the transcription starting point of Nestin. In addition, LncRNA ENST869 did not directly interact with Nestin protein to affect its activity. In conclusion, our results demonstrated that LncRNA ENST869 could affect the function of Nestin in breast cancer cells treated with Chidamide. Nestin is a key player in influencing the pharmacological activity of Chidamide and an essential factor in drug resistance of breast cancer cells.

LncRNA BC083743 Silencing Exacerbated Osteoporosis by Regulating the miR-103-3p/SATB2 Axis to Inhibit Osteogenic Differentiation

“…lncRNAs are structurally diverse and functionally complex and make a momentous part in biological development including genomic imprinting, cell cycle adjustion, cell multipotency, dosage compensation effects, reverse transcription translocon reticence, and chromosome telomere extending [ 7 ]. lncRNAs regulate a variety of human physiological and pathological processes by mediating chromatin modifications, regulating transcriptional processes, and mediating posttranscriptional control [ 8 , 9 ]. This in turn affects the course of osteosarcoma [ 10 ], osteoarthritis [ 11 ], degenerative disc disease [ 12 ], and other bone and joint diseases.…”

Integrated Analysis of Long Non-Coding RNA Expression Profiles in Glaesserella parasuis-Induced Meningitis: New Insight into Pathogenesis

“…Trans regulation and cis regulation were used to predict target genes. For the transacting prediction, in the adoption database, blast was first used to select the sequences with complementary or similar sequences, and then RNAplex [22] was utilized to calculate the complementary energy between the two sequences and select the sequences above the threshold (identity > 85%, e value < 1 × 10 −20 ). For the cis-acting prediction, coding genes with a distance of <100 bp to lncRNAs were screened.…”