METTL3 promotes proliferation and migration of colorectal cancer cells by increasing SNHG1 stability.

N6­methyladenosine (m6A) serves an essential role in RNA modulation and is implicated in multiple malignancies, including colorectal cancer (CRC). Methyltransferase­like 3 (METTL3) is an important writer in m6A modification, however its role in CRC in modifying small nucleolar RNA host gene 1 (SNHG1), an oncogenic long noncoding RNA, remains unclear. In the present study, METTL3 expression in CRC was assessed using online bioinformatics analysis, immunohistochemistry staining, western blotting, reverse transcription (RT)­quantitative PCR (qPCR) and cell transfections. Cell proliferation, migration and invasion were determined using functional Cell Counting Kit­8 (CCK­8) and Transwell assays. SNHG1 expression in CRC was evaluated using online bioinformatics analysis and RT­qPCR. Methylated RNA immunoprecipitation qPCR was performed to assess m6A modification changes of SNHG1 mRNA. The present study demonstrated that METTL3 is upregulated in CRC tissues and cell lines. Moreover, METTL3 expression was associated with several unfavourable clinical features in patients with CRC, including the stage of lymph node metastases and overall survival. Functional Transwell and CCK­8 assays demonstrated that knockdown of METTL3 suppressed CRC cell proliferation and migration. Furthermore, METTL3 was positively correlated with SNHG1 in CRC tissue, as indicated by analysis of data from The Cancer Genome Atlas. Mechanistically, SNHG1 contains 18 m6A modification sites. Through cell transfections and actinomycin D assays, the present study found that METTL3­mediated m6A modification at these sites enhances the stability of SNHG1 in CRC cells. Finally, it was demonstrated that SNHG1 knockdown partially diminished the facilitative effect of METTL3 on CRC cell migration and proliferation. The present study concluded that METTL3, a potential biomarker for assessing overall survival and metastasis in CRC, may serve as an oncogene, promote SNHG1 m6A modification, improve the stability of SNHG1 and enhance SNHG1­mediated oncogenic function in CRC.

Research progress of integrated traditional Chinese and Western medicine in the treatment of advanced gastric cancer.

Gastric cancer (GC) is a malignant tumor originating from the gastric epithelium, and its incidence and mortality rates rank third among all malignant tumors worldwide. It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice. However, with the advancements in medical technology and informatics, the values of traditional Chinese medicine (TCM) in preventing and treating GC and improving prognosis have increasingly been recognized. According to TCM, clinical manifestations of GC can be divided into Yege (dysphagia), regurgitation, stomach pain, and Zhengxia (abdominal mass). Due to the unbalanced distribution of health care resources in China, most GC patients already have progressive or advanced-stage disease at the first diagnosis. As a result, most GC patients have poor physical function, and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life. In contrast, TCM therapies have shown promising efficacy in the management of these patients. Here we review the role of the integrated TCM and Western medicine in treating advanced GC.

Biglycan up-regulated vascular endothelial growth factor (VEGF) expression and promoted angiogenesis in colon cancer.

Biglycan is an important component of the extracellular matrix, which belongs to the small leucine-rich proteoglycan family. Recent studies have shown that biglycan expression is elevated in many tumor tissues and implies poor prognosis, such as colon cancer. However, the molecular mechanism of biglycan in colon cancer has not been investigated. The present study aimed to investigate the effects of biglycan on vascular endothelial growth factor (VEGF) expression in colon cancer cells and on tumor angiogenesis in vivo. Biglycan overexpression vectors were constructed, and the stable biglycan overexpression in human colon cancer cell lines (HCT116 cells) was established by G418 screening. The stable cell clones were subsequently used to initiate tumor xenografts in nude mice. Our results showed that biglycan overexpression notably up-regulated the levels of VEGF in colon cancer cells, which was further confirmed by immunohistochemistry analysis in the xenograft colon tumors. Moreover, high levels of biglycan promoted angiogenesis and colon tumor growth, as evidenced by the increased cell viability, colon tumor size, and weight, as well as the CD34 expression. Additionally, we found that the extracellular signal-regulated kinase (ERK) signaling pathway was activated by biglycan in colon cancer cells. The ERK inhibitor PD98059 dramatically reversed the increased expression of VEGF induced by biglycan. Taken together, our results indicated that biglycan up-regulated VEGF expression in colon cancer cells and promoted tumor angiogenesis. Biglycan-mediated VEGF regulation may correlate with the activation of the ERK signaling pathway. Therefore, biglycan may be a promising target for anti-angiogenic therapy for cancer.

XPC gene intron 11 C/A polymorphism is a predictive biomarker for the sensitivity to NP chemotherapy in patients with non-small cell lung cancer.

The fact that intron single nucleotide polymorphisms could regulate gene expression or even alter gene expression levels has been the focus of attention. To study the relationship between the intron 11 C/A single nucleotide polymorphism of XPC gene and the efficacy of vinorelbine and cisplatin (NP) chemotherapy, 164 patients with non-small cell lung cancer (NSCLC) taking NP chemotherapy drugs were evaluated according to the efficacy of the treatment. We used polymerase chain reaction restriction fragment length polymorphism to examine the C/A polymorphism in the XPC gene intron 11 of the DNA samples extracted from peripheral blood. It was found that the frequency of patients in the effective group with C/C+C/A genotype (37.6%) had significant difference to chemotherapy than that of patients with A/A homozygotes (27.7%) in the same group (P=0.043, odds ratio=2.366, 95% confidence interval=1.026-5.457). Therefore, NSCLC patients with the C/C+C/A genotype are more sensitive to NP treatment than those with the A/A genotype. The XPC gene intron 11 C/A polymorphism may be a predictive biomarker for sensitivity to NP chemotherapy in patients with NSCLC.