Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1437
Peer-review started: October 13, 2023
First decision: December 8, 2023
Revised: December 19, 2023
Accepted: January 17, 2024
Article in press: January 17, 2024
Published online: April 15, 2024
Processing time: 181 Days and 0.8 Hours
Tumor metastasis, the high heterogeneity of cancer cells, and chemotherapy resistance are primary factors that contribute to the poor overall prognosis of gastric cancer (GC). However, its role in GC treatment is constrained by adverse drug reactions and drug resistance. In the realm of exploring alternative cancer treatments, natural compounds with anticancer properties, such as curcumin, are garnering attention because of their low adverse effects. Although the anticancer effects of curcumin have been extensively studied, its specific mechanisms of action remain incompletely understood. This study employs long non-coding RNA (lncRNA) sequencing to screen for differentially expressed lncRNAs after curcumin treatment. Further investigation will explore the relationship between the ability of curcumin to inhibit GC cells and lncRNA AC022424.2.
Recent studies have highlighted the association between abnormal lncRNA expression and various aspects of gastric cancer, including early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis. A comprehensive understanding of how lncRNAs intricately influence gastric cancer development can offer new perspectives for precision treatment and personalized management of gastric cancer patients. This study aims to uncover the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating the initiation and progression of gastric cancer.
The objective of this study was to identify curcumin-associated lncRNAs and examine the involvement of lncRNA AC022424.2 in the modulation of gastric cancer cell apoptosis, proliferation, and invasion upon curcumin treatment. Additionally, the validation of these findings was conducted using clinical samples.
The study used CCK-8 assays to assess curcumin's impact on gastric cancer cells, employing flow cytometry, scratch/Transwell assays, and western blotting to examine apoptosis, migration, invasion, and protein expression changes. LncRNA sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) validated differential expression before/after curcumin treatment in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown cells were generated to scrutinize lncRNA AC022424.2's effects on apoptosis, proliferation, migration, and invasion, with western blotting assessing pathway-related protein changes. RT-PCR measured lncRNA AC022424.2 expression in clinical gastric cancer tissues, correlating with pathological characteristics.
Curcumin induced gastric cancer cell apoptosis and inhibited proliferation, migration, and invasion in a dose- and time-dependent manner. Following curcumin treatment, lncRNA AC022424.2 was upregulated, and its knockdown intensified cancer cell aggressiveness. The impact of lncRNA AC022424.2 on cancer cells may involve the PI3K/Akt/mTOR and NF-κB signaling pathways. The downregulation of lncRNA AC022424.2 was associated with lymph node metastasis, suggesting its potential as a diagnostic and prognostic marker.
Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment.
The subsequent validation of these experimental results in clinical tissue specimens and exploration of specific mechanisms will provide more theoretical support for elucidating the role of lncRNAs in the occurrence and development of GC and identifying precise therapeutic targets.