Dysregulated genes and miRNAs in the apoptosis pathway in colorectal cancer patients

Slattery, Martha L.; Mullany, Lila E.; Sakoda, Lori C.; Wolff, Roger K.; Samowitz, Wade S.; Herrick, Jennifer S.

doi:10.1007/s10495-018-1451-1

Cited by 79 publications

(62 citation statements)

References 36 publications

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“…Similarly, miR-145 expression has been associated with improved patient survival in other cancers, including esophageal squamous cell carcinoma and cervical cancer, suggesting a wider tumor suppressor role for miR-145 [25,26]. Ectopic expression of miR-145 decreased breast cancer cell proliferation and increased apoptosis in colorectal cancer cell lines [27,28]. Similarly, we observed a significant increase in apoptosis in our neuroblastoma cell lines following over-expression of miR-145 in vitro.…”

Section: Discussionsupporting

confidence: 72%

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

Zhao

Zhou

et al. 2020

Bioengineered

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Neuroblastoma (NB) is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). It is well known that miR-145 functions as a tumor suppressor in several types of cancer. However, the impact of miR-145 on NB is still ambiguous. Our aim was to investigate the potential tumor suppressive role and mechanisms of miR-145 in high-risk neuroblastoma. Expression levels of miR-145 in tissues and cells were determined using RT-qPCR. The effect of miR-145 on cell viability was evaluated using MTT assays, apoptosis levels were determined using TUNEL staining, and the MTDH protein expression was determined using western blot and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting for MTDH. The results showed that miR-145 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and low miR-145 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-145 reduced cell viability and increased apoptosis in SH-SY-5Y cells. We identified MTDH as a direct target for miR-145 in SH-SY-5Y cells. Targeting MTDH has the similar results as miR-145 overexpression. Our findings suggest that low miR-145 expression was associated with poor prognosis in patients with NB, and the overexpression of miR-145 inhibited NB cells growth by down-regulating MTDH, thus providing a potential target for the development of microRNA-based approach for NB therapy.

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Section: Discussionsupporting

confidence: 72%

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

Zhao

Zhou

et al. 2020

Bioengineered

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“…Subsequently, a series of studies con rmed these results [8][9][10]. Decreased expression of these two miRNAs is involved in various cancer-related events, including proliferation, invasion, and migration, suggesting that they have anti-tumorigenic activity [11][12][13]. The KRAS oncogene is an important upstream mediator of the MAPK pathway, and its overexpression can lead to increased activation of the RAF/MEK/MAPK pathway, thereby promoting tumorigenesis [14].…”

Section: Introductionmentioning

confidence: 93%

Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival

Wang

Liu

Ren

et al. 2019

Preprint

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Background MicroRNAs have important roles in tumorigenesis. There is accumulating evidence of aberrant expression of miR-143 and miR-145 and their target gene KRAS has been described in colorectal cancer (CRC). We hypothesize that single nucleotide polymorphisms (SNPs) within or near mRNA-miRNA binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and promoting the development and progression of CRC.Methods We conducted a case-control study of 507 CRC cases recruited from a tertiary hospital and 497 population-based controls to assess the association of genetic polymorphisms in miR-143/145 and the KRAS 3′ untranslated region (3′ UTR) with CRC susceptibility and survival. Deaths and causes of death among the CRC cases were identified using the Hangzhou Cancer Registration System and Death Surveillance System. Genetic variations of genomic regions located from 500 bp upstream to 500 bp downstream of the miR-143/miR-145 gene and the 3′ UTR of KRAS were selected using the Haploview and HaploReg software. Results Using publicly available expression profiling data, we found that miR-143/145 and KRAS expression were all reduced in rectal cancer tissue compared with adjacent normal mucosa. The Rs74693964 C/T variant located 65 bp downstream of miR-145 genomic regions was observed to be associated with CRC susceptibility (adjusted odds ratio 2.414, 95% CI: 1.385–4.206). Among non-smokers, the miR-143 rs41291957 GA genotype and miR-145 rs74693964 CT genotype were borderline significantly associated with an increased risk of rectal cancer. However, there was no interaction effect between selected SNPs and smoking status. Cumulative effects of miR-143 and miR-145 on CRC risk were observed (Ptrend=0.03). CRC cases carrying variant genotype TT of KRAS rs712 had poorer survival (log-rank P=0.044, adjusted hazard ratio 4.328, 95% CI: 1.236–15.147). Conclusions Our results indicate that miRNA-related polymorphisms in miR-143/145 and KRAS are likely to be deleterious and represent potential biomarkers for CRC susceptibility and survival.

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“…The expression of survivin is higher during fetal development and in the majority of tumors, whereas it is completely absent in adults and in normal cells (17,28). Overexpression of survivin has been confirmed in breast, lung, ovarian, prostate and colon cancer (21,29). Expression of survivin has also been associated with poor prognosis and chemotherapy resistance (21,30,31).…”

Section: Discussionmentioning

confidence: 99%

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA‑218

et al. 2019

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Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker.

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Dysregulated genes and miRNAs in the apoptosis pathway in colorectal cancer patients

Cited by 79 publications

References 36 publications

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

MicroRNA-145 overexpression inhibits neuroblastoma tumorigenesis in vitro and in vivo

Association analysis of miRNA-related genetic polymorphisms in miR-143/145 and KRAS with colorectal cancer susceptibility and survival

Survivin is a prognostic indicator in glioblastoma and may be a target of microRNA‑218

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