Silencing of LINC01963 enhances the chemosensitivity of prostate cancer cells to docetaxel by targeting the miR-216b-5p/TrkB axis

Abstract

Docetaxel (DTX) treatment effectively prolongs the overall survival of patients with prostate cancer. However, most patients eventually develop resistance to chemotherapy and experience tumor progression or even death. Long noncoding RNAs (lncRNAs) affect docetaxel chemosensitivity. However, the biological role and regulatory mechanisms of lncRNAs in docetaxel-resistant prostate cancer remain unclear. Differences in lncRNAs were evaluated by lncRNA sequencing and evaluated using quantitative real-time polymerase chain reaction, and TrkB expression was measured through western blot analysis. Proliferation was measured using the MTS, while apoptosis and cell cycle were measured using flow cytometry. In addition, migration and invasion were measured using transwell assays. Forty-eight female BALB/c nude mice were used for subcutaneous tumorigenicity and lung metastasis assays. We found that LINC01963 was overexpressed in the PC3-DR cells. LINC01963 silencing enhanced the chemosensitivity of PC3-DR to docetaxel and inhibited tumorigenicity and lung metastasis, while LINC01963 overexpression enhanced the chemoresistance of PC3 cells to docetaxel. It was found that LINC01963 bind to miR-216b-5p. The miR-216b-5p inhibitor reversed the suppressive effect of sh-LINC01963 on PC3-DR cell proliferation, migration, and invasion. Furthermore, miR-216b-5p can bind to the 3′-UTR of NTRK2 and inhibit TrkB protein levels. TrkB enhances docetaxel resistance in prostate cancer and reverses the effects of LINC01963 silencing and miR-216b-5p overexpression. In conclusion, silencing LINC01963 inhibited TrkB protein level to enhance the chemosensitivity of PC3-DR to docetaxel by means of competitively binding to miR-216b-5p. This study illustrates that LINC01963 is a novel therapeutic target for treating prostate cancer patients with DTX resistance.

Lnc-SELPLG-2:1 enhanced osteosarcoma oncogenesis via hsa-miR-10a-5p and the BTRC cascade

“…MTS was conducted following previous research with a few revisions [22]. The cells were at the density of 1 × 10 6 /ml, and 100 μl/well were seeded into 96-well plates.…”

“…The detection of the cell cycle was performed in accordance with previous research with a few modifications [22]. PBS was used to harvest and wash the cells.…”

“…The apoptosis assay was performed in accordance with previous research with a few modifications [22].…”

“…Migration and invasion tests were conducted based on previous research with a few modifications [22]. Utilizing a 24-well plate with 8 μm pore size chamber inserts (Corning, USA), migration and invasion of tumor cells were evaluated.…”

“…Subcutaneous tumor formation in the nude mice were conducted following previous research with a few modifications [22]. The lnc-SELPLG-2:1 lentivirus was designed and acquired from Genepharma in Shanghai, China.…”