HER4 rs1595065 3'UTR Variant is a Possible Risk Factor for HER2 Positivity Among Breast Cancer Patients

Moradi, Bahareh; Tabatabaeian, Hossein; Sadeghi, Samira; Azadeh, Mansoureh; Ghaedi, Kamran

doi:10.5812/thrita.42195

Cited by 13 publications

(3 citation statements)

References 19 publications

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“…For instance, miR-9, miR-421, miR-27a, and miR-143 have been reported to be involved in the development and progression of the GC by regulating tumor cells proliferation, apoptosis, invasion, and metastasis ( 7 – 11 ). Regarding miR-3129, previous studies have demonstrated that it might be associated with the risk of cancers including colorectal and breast cancer ( 12 , 13 ). However, the role of miR-3129 in GC has not been demonstrated yet.…”

Section: Introductionmentioning

confidence: 99%

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

Yang¹,

Sheng²,

Pan³

et al. 2018

Braz J Med Biol Res

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Several microRNAs (miRNAs) have been reported as oncogenes or tumor suppressors in many cancers, including gastric cancer (GC). However, the role and molecular mechanism of miR-3129 in GC is largely unknown. We aimed to explore the function and the underlying molecular mechanism of miR-3129 in GC. Cancer tissues and corresponding adjacent tissues were collected from 50 patients with GC, and the expression of miR-3129 was detected by RT-qPCR. The expression of miR-3129 and pRb in human GC cell line SCG7091 was altered by transient transfection. Thereafter, MTT and flow cytometry assays were used to analyze cell viability and cell cycle. The expression of cyclin E, CDK2, CDK2 inhibitors (p16 and 21), and pRb were detected by RT-qPCR and western blot. A significant up-regulation of miR-3129 was observed in GC tissues compared to adjacent tissues. Overexpression of miR-3129 significantly improved cell viability after 4 days of post-transfection. Flow cytometry assay results showed that the miR-3129 overexpression arrested more SGC7901 cells at S phase. Moreover, overexpression of miR-3129 down-regulated the expression of CDK2 inhibitors while it up-regulated the expression levels of cyclin E, CDK2, and pRb. Interestingly, we found that pRb inhibition reversed the effect of miR-3129 inhibitor on cell proliferation in SGC7901 cells, increased cell viability, reduced cells at G0/1 phase, and modulated the expression of proliferation-related factors. Our results revealed that miR-3129 functioned as an oncogene through positive regulation of pRb and may prove to be a promising option for molecular therapy of GC.

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Section: Introductionmentioning

confidence: 99%

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

Yang¹,

Sheng²,

Pan³

et al. 2018

Braz J Med Biol Res

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“…However, no study has been conducted to investigate the role of MUC4 SNPs in gastric cancer. Among different polymorphisms, SNPs located at miRNA target sites may have an effect on mRNA stability and/or expression [10][11][12][13][14]; and therefore, they could be more functional.…”

Section: Introductionmentioning

confidence: 99%

miR-581-Related Single Nucleotide Polymorphism, rs2641726, Located in MUC4 Gene, is Associated with Gastric Cancer Incidence

et al. 2018

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MUC4 is aberrantly expressed in several carcinomas including breast, colon, ovarian, lung, prostate, stomach and pancreatic cancers. MUC4 can regulate cell apoptosis negatively and facilitate stomach tumorigenesis. In this research, we aimed to evaluate the possible association between rs2641726 (C [ A) polymorphism of MUC4 and gastric cancer risk in the Iranian population. In this case-control study, we collected blood samples from 168 gastric cancer patients and 66 healthy subjects. Allelespecific primer polymerase chain reaction method was applied to genotype rs2641726 in the obtained DNA samples. This study demonstrated that rs2641726 C allele was significantly associated with the incidence of gastric cancer, odds ratio = 3.382, 95% confidence interval: 1.840-6.217 (P \ 0.001). Furthermore, the distribution of this risk allele was highly enriched in the samples with stage III. In silico studies revealed that the C allele of rs2641726, located within MUC4 3 0 UTR, is potential to attenuate the interaction between miR-581 and MUC4 mRNA. This disturbing effect, which might result in higher expression of MUC4 oncoprotein, was proposed for the mechanism of action of the rs2641726 risk allele. rs2641726 C allele is significantly enriched in gastric cancer specimens. The attenuating effect of this allele on miR-581 and MUC4 interaction might be a potential mechanism of action by which C allele imposes its oncogenic impact.

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“…We have been investigating potential associations between miRNA-related polymorphisms and breast cancer in the Iranian population [22,[27][28][29][30][31][32][33]. Herein, we focused on the frequencies and predictive value of another ErbB4 3 0 -UTR SNP, rs12471583 (c.*3622A[G) in Iranian breast cancer patients.…”

Section: Introductionmentioning

confidence: 99%

ErbB4 3′-UTR Variant (c.*3622A>G) is Associated with ER/PR Negativity and Advanced Breast Cancer

et al. 2018

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A genetic variant may alter a gene expression level and as a result be associated with pathological characteristics in breast cancer. In this research, the frequency and association of the ErbB4 3 0 -untranslated region (3 0 -UTR) variant, rs12471583 (c.*3622A[G) was studied in an Iranian breast cancer patients. In silico assessment was performed to predict the function of the rs12471583 variant located on the 3 0 -UTR of ErbB4. Furthermore, as a casecontrol study, this polymorphism was genotyped in 243 breast cancer patients and non-cancerous controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The Armitage's trend test and regular association tests were performed to analyze a possible association between the rs12471583 and risk of breast cancer and its relevant pathological traits. The bioinformatics analysis predicted that the rs12471583 SNP is located on the four miRNA binding sites, including miR-511-5p, miR-4659a-5p, miR-4659b-5p, and miR-6830-3p. According to logistic regression tests, the G allele is negatively associated with ER-(OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), PR-(OR = 0.31, 95% C.I. = 0.10-0.98, p = 0.039), ER-/PR-(OR = 0.20, 95% C.I. = 0.04-0.93, p = 0.026), and advanced breast cancer (OR = 0.40, 95% C.I. = 0.18-0.85, p = 0.016). It has been found that ErbB4 expression may be linked to unfavorable outcomes in breast cancer. Likewise, our results suggest that the G allele may strengthen miRNA-ErbB4 binding efficiency and as a result reduce expression of ErbB4. This is a possible explanation for the observed association.

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HER4 rs1595065 3'UTR Variant is a Possible Risk Factor for HER2 Positivity Among Breast Cancer Patients

Cited by 13 publications

References 19 publications

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

miR-581-Related Single Nucleotide Polymorphism, rs2641726, Located in MUC4 Gene, is Associated with Gastric Cancer Incidence

ErbB4 3′-UTR Variant (c.*3622A>G) is Associated with ER/PR Negativity and Advanced Breast Cancer

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