ABSTRACT
BACKGROUND: Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression. AIM: To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples. METHODS: The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics. RESULTS: Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker. CONCLUSION: 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.
ABSTRACT
Circular RNAs (circRNAs) have recently emerged as novel and potentially promising therapeutic targets in a serious of cancers. However, the expression pattern and biological function of circRNAs in colon cancer remain largely elusive. This study firstly analyzed circRNA microarray of colon cancer and selected circ-0001313 as the study object. We aim to comprehensively investigate the expression pattern and biological function of circ-0001313 in the progression of colon cancer. Relative levels of circ-0001313 and miRNA-510-5p in colon cancer tissues and cell lines were determined with qRT-PCR. The binding relationship between miRNA-510-5p to circ-0001313 and AKT2 was predicted by bioinformatics analyses and further confirmed by dual-luciferase reporter gene assay. Regulatory effects of circ-0001313/miRNA-510-5p/AKT2 axis on colon cancer cells were evaluated by EdU assay and flow cytometry. Consistent with the microarray analysis, circ-0001313 was highly expressed in colon cancer tissues and cell lines. Knockdown of circ-0001313 attenuated proliferative ability, but induced apoptosis of colon cancer cells. Furthermore, we confirmed that circ-0001313 competitively bound to miRNA-510-5p, thus upregulating its target gene AKT2. Moreover, western blot analyses revealed that circ-0001313 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. In conclusion, our study revealed that circ-0001313 regulates the pathogenesis of colon cancer by sponging miRNA-510-5p to upregulate AKT2 expression.
ABSTRACT
BACKGROUND: Members of eukaryotic chaperonin family are essential for cell survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been implicated in the development of several types of cancers. However, the role of CCT3 in the development of gastric cancer has yet to be determined. METHODS: The expression patterns of CCT3 in the surgical specimens from 26 gastric cancer patients were evaluated using immunohistochemistry methods. To study the possible roles of CCT3 in the growth and survival of gastric cancer cells, RNA interference was used to knockdown CCT3 expression in gastric cancer cell lines BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation, apoptosis and in vivo growth were examined. Finally, gene expression changes related to CCT3 knockdown were studied using gene array analysis and western blotting. RESULTS: Higher level of CCT3 expression was detected in the gastric cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3 inhibited proliferation and colony formation while promoted apoptosis of gastric cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in nude mice when CCT3 expression was suppressed. Gene expression analysis showed that CCT3 knockdown was associated with down-regulation of mitogen-activated protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up-regulation of cyclin-dependent kinase 2 and 6. CONCLUSION: Our results suggested that CCT3 played a critical role in gastric cancer growth and survival. Further studies on the mechanisms of CCT3 function is mandated to develop novel cancer treatment targeting CCT3.
ABSTRACT
The goal of this study is to present the multiple institutions experience comparing the outcome of management between initial laparoscopic cholecystectomy (LC) surgeon and specialist as well as the outcome of different operative procedures to major bile duct injury (BDI) after LC. We have retrospectively collected data of 77 cases of perioperatively detected major BDI in LC at 15 general surgical institutions from 1997 to 2007. We classified 42 cases treated by an experienced biliary surgeon as Group A and 35 cases treated by the initial LC surgeon as Group B. Forty-eight cases were treated with duct-to-duct anastomosis as Group C and 29 cases were treated with Roux-en-Y choledochojejunostomy as Group D. The median duration of follow-up was 62 months. The outcome of groups was compared. In Group A, 7 of 42 (16.7%) patients developed a failure. Two of seven (28.6%) patients were treated by a secondary operation. In Group B, 24 of 35 (68.6%) patients developed a failure. Seventeen of 24 (70.8%) patients were treated by a secondary operation. One of 35 (2.85%) patients died. The significant differences were observed in failure and secondary operations (16.7 vs 68.6%, P < 0.01 and 28.6 vs 70.8%, P < 0.01). There is no significant difference Group C and Group D in failure rate (28.5 vs 11.7%, P > 0.05). A multiple institutional cooperative methodology between the local surgical institution and tertiary care centers provided a good way to limit further operations, failure. The reconstructive strategy is important and should be selected according to the type of injury and the diagnosed status of major BDI.
