Accumulating evidence has revealed that aberrantly expressed long non-coding transcripts are involved in the development and progression of colorectal cancer (CRC). Small nucleolar RNA host gene 3 (SNHG3) is a newly identified lncRNA, and little is known about its clinical significance and biological functions in the development of CRC. In the present study, we found that the expression of SNHG3 was significantly upregulated in CRC, and upregulation of SNHG3 predicted poor prognosis for patients with CRC as determined through analysis of the data obtained from TCGA database. Gain-of function and loss-of function assays revealed that SNHG3 markedly promoted cellular proliferation of CRC cells. Gene Set Enrichment Analysis (GSEA) suggested that high expression of SNHG3 was positively associated with c-Myc and its targets genes. Furthermore, ectopic overexpression of SNHG3 increased the expression of c-Myc and its target genes, whereas inhibition of SNHG3 had opposite effect on the expression of c-Myc and its targets. Mechanistic investigations demonstrated that SNHG3 functioned as a competing endogenous RNA (ceRNA) to ‘sponge’ miR-182-5p, thus leading to the release of c-Myc from miR-182-5p and modulating the expression of c-Myc. In conclusion, SNHG3 promoted CRC progression via sponging miR-182-5p and upregulating c-Myc and its target genes.
MicroRNAs have been suggested as potential regulators in gastric cancer (GC) development through affecting the expression of their target genes. Previous studies have demonstrated that miR-140-5p is downregulated in GC. However, the underlying functional role of miR-140-5p in GC remains largely unknown. The present study revealed that miR-140-5p expression was significantly decreased in 60 GC tissues, compared with corresponding adjacent non-tumor tissues. A lower miR-140-5p expression was significantly associated with lymph node metastasis and an advanced Tumor-Node-Metastasis stage in patients with GC. Furthermore, patients with a lower miR-140-5p expression exhibited shorter disease-free survival and overall survival times. Gain- and loss-of-function assays revealed that increased miR-140-5p expression significantly inhibited GC cell proliferation and invasion ability, as well as the Wnt/β-catenin signaling pathway by decreasing WNT1 and β-catenin expression. However, decreasing miR-140-5p expression had the opposite effects. Bioinformatics methods and dual-luciferase reporter assays revealed that WNT1 was a direct target of miR-140-5p. miR-140-5p suppressed cell proliferation and invasion by regulating WNT1 expression. Therefore, the results of the present study demonstrated that miR-140-5p may serve as a potential prognostic marker and therapeutic target in patients with GC.
What is known and objectives The optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co‐therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS‐mutant mCRC (as defined by mutations in KRAS and NRAS exons 2–4)controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks. Methods We retrospectively analysed patients with RAS‐mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis. Results and discussion The median progression‐free survival (mPFS)of patients was 9.0 months (95% CI 8.0–10.0) in the observation group and 7.2 months (95% CI 6.0–8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects. What is new and conclusion Bevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.
Purpose: MicroRNA (miRNA) plays significant role in the development and progression of cancer. We aimed to identify miRNA signatures to be used as diagnostic and prognostic biomarkers in non-small-cell lung cancer (NSCLC). Experimental Design: Patients with NSCLC who underwent surgical resection and didn't receive any therapy before surgery were randomly divided into training set (198 patients) and test set (199 patients). The miRNA expression levels were detected by microarray and selected miRNAs were verified by quantitative real-time PCR (qRT-PCR). The other 302 patients from another center were used as an independent set to verify the miRNA signature. Results: A 37-miRNA signature consisting of 15 downregulated miRNAs and 22 upregulated miRNAs was established for distinguishing NSCLC specimens from noncancerous lung tissues in the training set with 98.2% accuracy. In the test set, the classification accuracy of the signature was 98.5%. Then three miRNAs were chosen to construct prognostic signature in the training set. A formula based on the 3 miRNAs was built to calculate prognostic index. Kaplan-Meier analysis showed that patients with a high prognostic index had a significant poorer survival than those with a low index. The 3-miRNA signature was validated in test set with the same formula for computing the prognostic index. The expression levels of 4 miRNAs including the 3 miRNA in the prognostic signature were verified by RT-PCR in 33 paired NSCLC and corresponding noncancerous lung tissues. The expression level of the 3 miRNA was detected by qRT-PCR in the independent set. Survival analysis showed that the 3-miRNA signature was associated with survival in the independent set. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic biomarker. A combination of the 3-miRNA signature and TNM stage had much better prognostic ability than did TNM stage alone in the training, test and independent sets. Conclusions: The 37-miRNA and 3-miRNA signatures identified in our study may be useful biomarkers for diagnosis and prognosis of NSCLC patients. Note: This abstract was not presented at the meeting. Citation Format: Heng-Ying Pu, Da Fu, Mei-Yin Zhang, Yin-Lian Cha, Hai-Shan Peng, Lan-Jun Zhang, Wei-Hua Jia, Yi-Xin Zeng, Wan-Qing Liu, Steven X.F. Zheng, Guo-Hong Hu, Hui-Yun Wang. Prognostic value of microRNA signature in non-small-cell lung cancer: A microRNA expression analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5223. doi:10.1158/1538-7445.AM2014-5223
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