Messenger RNA

Internal medicine

Receptor

Autophagy

Taurine

Insulin-like growth factor

Colorectal cancer

Biology

Gene

Cancer

Endocrinology

Apoptosis

Chemistry

Insulin resistance

Growth factor

Chemotherapy

Insulin

Cisplatin

Cell biology

Cancer research

Amino acid

Biochemistry

Medicine

Bioengineered

Long non-coding RNAs (lncRNAs) have been demonstrated to influence the chemoresistance of colorectal cancer (CRC). Therefore, the study is designed to investigate the regulatory function and mechanism of Taurine up-regulated gene 1 (TUG1) in the cisplatin resistance of CRC. qRT-PCR checked the expressions of TUG1, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and miR-195-5p in CRC tissues and cells. The TUG1 or miR-195-5p overexpression model was engineered in CRC cells, followed by treatment with DDP or the autophagy inhibitor (Chloroquine, CQ). CCK8 (Cell Counting Kit-8) and the colony formation experiment monitored cell proliferation. Flow cytometry examined apoptosis, Transwell tracked migration and invasion, and Western blot ascertained the protein profiles of autophagy proteins (LC3I/LC3II and Beclin1) and the HDGF/DDX5/β-catenin pathway. Dual-luciferase gene reporter assay and RNA immunoprecipitation confirmed the binding correlation between TUG1 and miR-195-5p and between miR-195-5p and HDGF. Furthermore, in-vivo experiments in nude mice probed the function and mechanism of IGF2BP2 in CRC cell growth. The profiles of TUG1 and IGF2BP2 were elevated in CRC tissues, and IGF2BP2 enhanced TUG1's expression in CRC cells. TUG1 activated autophagy to facilitate CRC cells' resistance to DDP. TUG1 targets miR-195-5p, and miR-195-5p targets HDGF. Overexpression of miR-195-5p abated the cancer-promoting function of TUG1 and curbed the profile of the HDGF/DDX5/β-catenin axis. TUG1 stabilized by IGF2BP2 boosted CRC cell proliferation, migration, migration, and autophagy via the miR-195-5p/HDGF/DDX5/β-catenin axis, hence enhancing CRC cell's resistance to DDP.

Insulin-like growth factor 2 mRNA-binding protein 2-stabilized long non-coding RNA Taurine up-regulated gene 1 (TUG1) promotes cisplatin-resistance of colorectal cancer via modulating autophagy