长链非编码RNA MIR600HG作为一种竞争性内源RNA，通过调控miR-1197/PITPNM3轴抑制胰腺癌进展。

Long non-coding RNA MIR600HG as a ceRNA inhibits the pancreatic cancer progression through regulating the miR-1197/PITPNM3 axis.

作者信息

Yang Baoming, Jiao Zhikai, Feng Ningning, Zhang Yueshan, Wang Shunxiang

机构信息

Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

出版信息

Heliyon. 2024 Jan 19;10(2):e24546. doi: 10.1016/j.heliyon.2024.e24546. eCollection 2024 Jan 30.

DOI:10.1016/j.heliyon.2024.e24546

PMID:38312687

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10834820/

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.

摘要

目的

胰腺癌（PC）被认为是一种预后较差的高恶性肿瘤。长链非编码RNA（lncRNAs）是预测癌症预后的潜在因素。MIR600HG在PC中的作用有待进一步研究。我们的工作主要聚焦于MIR600HG对PC预后的重要性及其调控PC进展的潜在分子机制。

方法

从TCGA数据库获取数据集，以发现PC中MIR600HG的差异表达基因和预后意义，并构建MIR600HG竞争性内源RNA（ceRNA）。收集临床标本以验证分析结果。转染过表达MIR600HG的载体，研究MIR600HG在增殖、凋亡、侵袭和迁移中的作用。使用CCK-8、流式细胞术、Transwell和划痕试验等方法来探究凋亡、迁移和侵袭情况。我们评估了增殖相关基因（PCNA、CyclinD1和P27），以及侵袭和迁移相关基因，如MMP-9、MMP-7和ICAM-1。通过荧光素酶报告基因试验确定MIR600HG与miR-1197/PITPNM3轴之间的转录调控。

结果

在本研究中，PC组织和细胞中MIR600HG均下调，且MIR600HG下调与PC患者不良临床结局密切相关。MIR600HG可抑制PC细胞的增殖、迁移和侵袭。我们还研究了MIR600HG是否作为微小RNA-1197（miR-1197）的海绵，以及miR-1197是否作用于PITPNM3。我们发现MIR600HG与PITPNM3呈正相关，而miR-1197与MIR600HG（或PITPNM3）呈负相关。此外，MIR600HG过表达（MIR600HG-OE）后，PITPNM3的mRNA和蛋白表达同时增加，但在MIR600HG-OE细胞和miR-1197模拟物中，这一结果部分减弱。