Mir-26b inhibits growth and resistance to paclitaxel chemotherapy by silencing the CDC6 gene in gastric cancer

Abstract

A b s t r a c tIntroduction: Gastric cancer is one of the most common cancers of the digestive system and is associated with high morbidity and mortality. The aim of this study was to investigate whether miR-26b is involved in the proliferation and resistance to paclitaxel chemotherapy in gastric cancer cells. Material and methods: The expression of miR-26b in gastric cancer cell lines was determined by quantitative real-time PCR. Bioinformatics software was used to predict potential target genes of miR-26b. Luciferase assay was used to verify the interactions between target genes and miR-26b. CDC6 protein expression was measured by Western blot. The proliferation and chemotherapy resistance were analyzed by MTT assay. Cell invasion was evaluated by Transwell assay. Results: MiR-26b was down-regulated in gastric cancer cell lines compared to normal control cells, and its expression in drug resistance cells was even lower (p < 0.05). CDC6 was identified as a potential target gene of miR-26b by using bioinformatics analysis software. The expression of CDC6 was inhibited by miR-26b both at RNA level, which was determined by luciferase assay, and at protein level, which was determined by Western blot (p < 0.05). Silencing CDC6 inhibited cell proliferation, invasion, and promoted apoptosis of gastric cancer cell lines, BGC823 and SGC7901 (p < 0.05). Moreover, CDC6 knockdown inhibited chemotherapy resistance to paclitaxel, IC50 to paclitaxel decreased from 153.17 ±0.49 μg/l to 39.81 ±0.28 μg/l (p < 0.05). Conclusions: miR-26b inhibits growth and resistance to paclitaxel chemotherapy by silencing the CDC6 gene in the gastric cancer cell line SGC7901.

<p>Potential Prognostic and Diagnostic Values of CDC6, CDC45, ORC6 and SNHG7 in Colorectal Cancer</p>

“…30 In addition, CDC6 may be a promising target for overcoming CDDP resistance in bladder cancer, 31 oxaliplatin resistance for CRC 32 and paclitaxel resistance for gastric cancer. 33 As a DNA replication initiation factor, Cdc45 directly interacts with MCM7 and DNA polymerase alpha in the assembly of the highly conserved multiprotein complex that includes Cdc6/Cdc18, the MCMs, and DNA polymerase; the assembly of the complex is essential for the initiation of eukaryotic DNA replication. [28][29][30] CDC45 might be the target of miR-34a and a potential therapeutic target of CRC.…”

Circular RNA (circ‐0075804) promotes the proliferation of retinoblastoma via combining heterogeneous nuclear ribonucleoprotein K (HNRNPK) to improve the stability of E2F transcription factor 3 E2F3

“…The novel microRNA miR‐CHA1 modulates lung cancer cell proliferation and apoptosis by targeting XIAP 10 . MiR‐26b suppresses gastric cancer cell growth by inhibiting the expression of CDC6 11 . E2F transcription factor 3 (E2F3) has been researched to be involved in the progression of cancer.…”

Systems biomedicine of primary and metastatic colorectal cancer reveals potential therapeutic targets

“…Cdc6 is considered as a potential therapeutic target in in BC patients [72]. Parallel to these findings, silencing the CDC6 gene by miR-26b in gastric cancer cell line SGC7901 leads to growth inhibition but resistance to paclitaxel-based chemotherapy [73]. Our results for expression of this gene in MvsP analysis are totally contradictory to the mentioned information although, no study directly measured the expression level of this gene in CRC samples, so further investigation is needed.…”