Long noncoding RNA H19 participates in metformin-mediated inhibition of gastric cancer cell invasion
Peiwen Li1,2, Linhao Tong1, Yongxi Song1
1Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang, China.
Abstract:
Recent research suggests that the first-line oral antidiabetes drug metformin may prevent gastric cancer progression and improve prognosis. Many studies have also shown that long noncoding RNAs (lncRNAs) play important roles in many biological processes. Therefore, we aimed to explore whether lncRNAs participate in the mechanisms by which metformin affects gastric cancer cells. In the current study, we found that metformin significantly inhibited the cellular functions of gastric cancer cells through Cell Counting Kit-8 and invasion assays. We found that lncRNA H19 was greatly downregulated in gastric cancer cells treated with metformin using lncRNA microassays. Based on bioinformatics analyses of the Oncomine and The Cancer Genome Atlas databases, H19 is shown to be overexpressed in gastric cancer tissues, with increased expression of H19 relating to advanced pathological tumor stage and pathological tumor node metastasis stage, indicating that H19 may be associated with the invasive ability of gastric cancer. We knocked down H19 in AGS and SGC7901 cell lines and found that knocked-down H19 could decrease gastric cancer cell invasion and that metformin could not further decrease invasion after the knock down. Moreover, H19 depletion increased AMPK activation and decreased MMP9 expression, and metformin could not further activate AMPK or decrease MMP9 in H19 knocked-down gastric cancer cells. In summary, metformin has a profound antitumor effect on gastric cancer cells, and H19 is a key component in the process of metformin suppressing gastric cancer cell invasion.
Insights
Metformin, an antidiabetes drug, inhibits gastric cancer progression by downregulating long noncoding RNA H19. This mechanism involves H19’s role in cell invasion and AMPK activation.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Metformin is a first-line oral antidiabetes drug with potential anticancer properties.
- Long noncoding RNAs (lncRNAs) are implicated in various biological processes, including cancer.
- The precise mechanisms by which metformin impacts gastric cancer, particularly involving lncRNAs, require further elucidation.
Purpose of the Study:
- To investigate the role of lncRNAs in metformin's effect on gastric cancer cells.
- To identify specific lncRNAs involved in metformin's anti-gastric cancer mechanisms.
- To explore the relationship between metformin, lncRNA H19, and gastric cancer cell functions.
Main Methods:
- Gastric cancer cell lines were treated with metformin.
- Cell Counting Kit-8 and invasion assays were performed to assess cellular functions.
- lncRNA microarrays were used to identify differentially expressed lncRNAs.
- Bioinformatic analyses utilized Oncomine and The Cancer Genome Atlas databases.
- H19 was knocked down in cell lines to evaluate its functional impact.
Main Results:
- Metformin significantly inhibited gastric cancer cell proliferation and invasion.
- lncRNA H19 was markedly downregulated in metformin-treated gastric cancer cells.
- H19 is overexpressed in gastric cancer tissues and correlates with advanced tumor stage and metastasis.
- Knockdown of H19 reduced gastric cancer cell invasion, and metformin's effect was diminished.
- H19 depletion increased AMPK activation and decreased MMP9 expression, with metformin showing no further effect.
Conclusions:
- Metformin exhibits significant antitumor effects on gastric cancer cells.
- lncRNA H19 is a crucial mediator in metformin's suppression of gastric cancer cell invasion.
- Targeting H19 may represent a therapeutic strategy in combination with metformin for gastric cancer.
More Related Videos
Related Concept Videos
02:36RNA Polymerase II Accessory Proteins
00:46Feedback Inhibition
01:16Gastric Emptying
01:16Gastric Motility
Peristaltic Waves and Chyme Formation
Upon food entry, the stomach initiates...
01:23RNA Interference
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:26Gastric Phase of Digestion
When food enters the stomach, it stretches the stomach walls and activates stretch receptors. This triggers local reflexes of the enteric nervous system, mediated through the myenteric plexus. These...