In recent years, microRNAs, also called as miRNAs, play an important role in carcinogenesis, and the dysregulation of miRNAs is closely associated with cancer progression. Till now, little has been known about the role of miRNA-146a in the esophageal squamous cell carcinomas (ESCC). In the present study, we used in vitro assays to investigate the mechanisms of miRNA-146a in ESCC cell lines and 60 ESCC tissues. Here, we found that miRNA-146a expression is downregulated in both ESCC cell lines and tissues and obviously associated with pathological indicators, such as metastasis and stage of ESCC. In addition, the overexpression of miRNA-146a suppressed EC109 and TE8 cell proliferation and invasion. Meanwhile, miRNA-146a overexpression extremely inhibited the protein expression of insulin receptor substrate 2 (IRS2). Notably, the enforced expression of IRS2 in EC109 cells with miRNA-146a overexpression attenuated the inhibitory effects of miRNA-146a. In conclusion, our findings suggest that miRNA-146a may function as a useful clinical tool in the treatment and diagnosis of ESCC, and its overexpression suppressed cell growth through inhibition of IRS2. Thus, miRNA-146a pathway may be recommended as potential makers for drug design.
In recent years, transforming growth factor-β (TGF-β) and the serine-arginine protein kinase 1 (SRPK1) have been recommended as a key signal mediator that is involved in oncogenesis. However, the mechanisms underlying TGF-β-SRPK1 pathway-mediated proliferation and apoptosis in the esophageal squamous cell carcinomas (ESCC) have not been well featured till now. We used immunohistochemistry, immunoblotting, and RT-PCR to assess the expression of SRPK1 in 120 cases of ESCC samples and cell lines. Subsequently, some in vitro assays were also applied where cells were administrated with TGF-β. We found that SRPK1 was highly expressed in ESCC tissues and acts as an independent prognostic factor for ESCC patients. In vitro studies indicated that overexpression of wild-type SRPK1 promoted ESCC cell proliferation, while overexpression of the kinase-dead mutant of SRPK1 or RNA interference against SRPK1 suppressed cell growth and enhanced apoptosis. The knockdown of SRPK1 also inhibited subcutaneous xenografts' growth of ESCC cells in nude mice. Furthermore, Western bolt analysis showed SRPK1 can activate Akt phosphorylation and inhibit JNK phosphorylation. In conclusion, SRPK1 mediates TGF-β-induced proliferation and apoptosis by regulating AKT and JNK in ESCC, which indicates TGF-β-SRPK1 pathway may be suggested as a useful target to affect the progression of ESCC.
The inhibition of Wisp-1 expression can reduce the proliferation, migration and adhesion of mouse hepatocellular carcinoma cells, which is related to the AKT/glycogen synthase kinase-3β pathway. Wisp-1 gene may be the potential target to cure the hepatocellular carcinoma.
Colorectal cancer (CRC) ranks the fifth leading cause of cancer death in China. EZH2 is a member of Polycomb-group (PcG) family and associated with transcriptional repression and cancer development. In this study, we report the association between a missense variant in EZH2 and risk of CRC. Through a systematic selection of variants in EZH2, we identified rs2302427 in the exon region of EZH2 and genotyped this variant in 852 CRC patients and 1,303 healthy controls using Taqman genotyping assay. The association between this variant and CRC risk was calculated using logistic regression with adjustment of sex, age, smoking status and drinking status. The result showed that rs2302427 was significantly associated with CRC susceptibility under an additive model (P=0.0068). Compared with CC genotype carriers, CG genotype and GG genotype carriers were associated with risk of CRC with odds ratio being 0.78 (95% CI: 0.63-0.96, P=0.0198) and 0.54 (95% CI: 0.24-1.18, P=0.1224), respectively. When stratified by sex, age, smoking status or drinking status, significant associations were observed only in younger individuals (OR=0.67, 95% CI: 0.50-0.89, P=0.0067) or smokers (OR=0.65, 95% CI: 0.48-0.88, P=0.0051). This study provides new insights into the personalized prevention of colorectal cancer.
Background: Chemotherapy is the main treatment for metastatic triple-negative breast cancer (mTNBC). However, mTNBC patients (pts) is often associated with chemotherapy resistance and poor prognosis. Biomarkers that can effectively predict the efficacy of chemotherapy for mTNBC are currently lacking. Detection of circulating tumor DNA (ctDNA) in plasma by liquid biopsy is a minimally invasive and highly sensitive method, which has been wildly used in the clinic and plays an important role in tumor diagnosis, efficacy evaluation, residual and recurrent tumor detection, etc. But yet, the clinical application of ctDNA in mTNBC remains relatively scarce. Here, for the first time, we set to explore the possibility of ctDNA as a biomarker for predicting chemotherapy response and prognosis in mTNBC.Methods: From May 2018 to October 2020, 38 mTNBC pts who received less than 3rd line standard chemotherapy were prospectively included. Tumor tissues were obtained prior chemotherapy, and plasma for ctDNA were collected at baseline, a day before the 3rd cycle chemotherapy and at disease progression. Next-generation sequencing (NGS,457 genes panel) was performed on all samples for mutation detection. And the ctDNA fraction, maximum variant allele frequency (max-VAF), tumor mutation burden (TMB) and other variate were calculated, further combined with clinical data, chemotherapy response and survival of pts for statistical analysis.Results: Finally, 109 blood samples and 13 tissue samples were detected by NGS. A total of 214 mutation genes and 397 mutation sites were detected. The mutation types included missense mutation, nonsense mutation, non-/frameshift insertion, non-/frameshift deletion, non-/frameshift substitution, splicing mutation and so on. The genes with the top 5 mutation frequencies were TP53 (32/38, 84.21%), PIK3CA (14/38, 36.84%), KMT2C (8/38, 21.05%), PTEN (6/38, 15.79%), NOTCH4 (6/38, 15.79%), respectively. The same variants were identified in 12 of 13 pts in paired plasma and tissue, with a concordance rate of 92.3%. The mutation rate in plasma ctDNA was significantly lower than that in tissues (15.26% ± 12.52% vs. 28.88 ± 16.54%, P < 0.001) but was still positively correlated with that in tissues (r = 0.306, P = 0.049). The median progression-free survival (mPFS) of pts with GNAS mutation was shorter than GNAS wild-type pts (3.000 vs. 6.100 months, P = 0.014). The area under curve of ctDNA fraction (0.812, P = 0.043), max-VAF (0.817, P = 0.043) and TMB (plasma) (0.759, P = 0.053) in predicting chemotherapy resistance or disease progression were larger than CEA (0.491, P = 0.888), CA125 (0.574, P = 0.243) and CA153 (0.482, P = 0.778). CtDNA fraction (r = 0.482, P < 0.001), max-VAF (r = 0.489, P < 0.001), TMB (plasma). (r = 0.419, P < 0.001) were correlated with chemotherapy response measured by RECIST v1.1 in CT imaging, while CEA (r = -0.024, P = 0.808), CA125 (r = 0.111, P = 0.266) and CA153 (r = -0.017, P = 0.865) had no correlation with chemotherapy response. The mPFS of pts with ctDNA fraction ≤ 50% or max-VAF ≤ 0.4 at baseline was significantly longer than that of pts with ctDNA fraction > 50% (6.100 vs. 3.430 months, P = 0.006) or max-VAF > 0.4 (6.100 vs. 3.430 months, P = 0.047). The elimination of mutations or the decrease of mutation rate in plasma ctDNA after 2 cycles of chemotherapy showed better chemotherapy response, while recurrence of mutations, increase of mutation rate and emergence of new mutations showed chemotherapy resistance.Conclusions: Mutations in tumor tissues and plasma ctDNA of mTNBC pts detected by NGS have high consistency. And compared with CT imaging and traditional tumor markers, dynamic monitoring ctDNA can more aptly reflect the change of whole-body tumor burden, better predict the chemotherapy response and prognosis in mTNBC. Citation Format: Huihui Li, Yajing Chi, Sha Yin, Bo Yu, Mu Su, Baoxuan Zhang, Ling Qiang, Guohua Ren, Lihua Song, Bing Bu, Shu Fang, Mao Shang, Qiaorui Tan, Xiaochu Man. Dynamic monitoring of circulating tumor DNA can predict chemotherapy response and prognosis in metastatic triple-negative breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-27.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.