Heliyon (Jan 2024)
Long non-coding RNA MIR600HG as a ceRNA inhibits the pancreatic cancer progression through regulating the miR-1197/PITPNM3 axis
Abstract
Objective: Pancreatic cancer (PC) is considered to be a highly malignant cancer with poor prognosis. Long non-coding RNAs (lncRNAs) is the potential factor to predict cancer prognosis. The effect of MIR600HG in PC needs to be further studied. Our work mainly focused on the importance of MIR600HG for PC prognosis and its underlying molecular mechanism of regulating PC progression. Methods: Data set was acquired from TCGA database to find differentially expressed genes and prognostic significance of MIR600HG in PC, and to construct the MIR600HG competitive endogenous RNA (ceRNA). Clinical specimens were collected to prove the analysis results. Vector over-expressed MIR600HG was transfected to study the roles of MIR600HG in proliferation, apoptosis, invasion and migration. The methods of CCK-8, flow cytometry, Transwell and scratch assays were all used in order to explore the apoptosis, migration and invasion. We evaluated the proliferation-related genes (PCNA, CyclinD1 and P27), as well as invasion and migration-related genes such as MMP-9, MMP-7 and ICAM-1. The transcriptional regulation between MIR600HG and miR-1197/PITPNM3 axis was determined with luciferase reporter assays. Results: In present study, MIR600HG was dropped in both PC tissues and cells, and the down-regulated MIR600HG was closely related to the poor clinical outcomes in PC patients. MIR600HG could inhibit proliferation, migration and invasion in PC cells. We also investigated whether MIR600HG acting as a sponge of microRNA-1197 (miR-1197) and miR-1197 acting on PITPNM3. We found the positive association between MIR600HG and PITPNM3, as well as the negative association of miR-1197 and MIR600HG (or PITPNM3). Moreover, PITPNM3 mRNA and protein expression saw a simultaneous increase after the MIR600HG-overexpression (MIR600HG-OE), but this result partially diminished in MIR600HG-OE cells and miR-1197 mimics. Conclusions: Our study explored the anticancer action of MIR600HG in PC by regulating miR-1197 to increase the expression of PITPNM3, which might help the diagnosis and therapy of PC.
