Identification of new miRNA biomarkers associated with HER2-positive breast cancers

Tashkandi, Hossam; Shah, Nirav R.; Patel, Yogin; Chen, Hexin

doi:10.18632/oncoscience.275

Cited by 20 publications

(11 citation statements)

References 27 publications

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“…Two miRNAs identified in our cohort-miR-30d and mir-195-5p-inhibit the cell cycle by targeting cyclin E [28,29]. Consistently, their lower expression was noted in biologically aggressive types of breast cancer, i.e., HER2-enriched and basal-like carcinomas [30]. As expected, G1/S transition of mitotic cycle and regulation of cell cycle were identified in the top 20 GO BP categories predicted as miRNA targets in our study.…”

Section: Discussionsupporting

confidence: 87%

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers Is Mainly Dependent on HER2 Status—A Pilot Study

et al. 2020

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Estrogen (ER) and progesterone (PgR) receptors and HER2 are crucial in the assessment of breast cancer specimens due to their prognostic and predictive significance. Single hormone receptor-positive breast cancers are less common and their clinical course is less favorable than ER(+)/PgR(+) tumors. Their molecular features, especially microRNA (miRNA) profiles, have not been investigated to date. Tumor specimens from 36 chemonaive breast cancer patients with known ER and PgR status (18 ER(+)/PgR(−) and 18 ER(−)/PgR(+) cases) were enrolled to the study. The expression of 829 miRNAs was evaluated with nCounter Human v3 miRNA expression Assay (NanoString). miRNAs differentiating between ER/PgR/HER2 phenotypes were selected based on fold change (FC) calculated for the mean normalized counts of each probe in compared groups. The differences were estimated with Student’s T-test or Two-Way ANOVA (considering also the HER2 status). The results were validated using The Cancer Genome Atlas (TCGA) dataset. Following quality control of raw data, fourcases were excluded due to low sample quality, leaving 14 ER(+)/PgR(−) and 18 ER(−)/PgR(+) cases. After correction for multiple comparisons, we did not find miRNA signature differentiating between ER(−)/PgR(+) and ER(+)/PgR(−) breast cancers. However, a trend for differing expression (p-value ≤ 0.05; FDR > 0.2; ANOVA) in eight miRNAs was observed. The ER(+)/PgR(−) group demonstrated elevated levels of four miRNAs—miR-30a-5p, miR-29c-3p, miR-141-3p and miR-423-5p—while the ER(−)/PgR(+) tumors were enriched in another four miRNAs—miR-514b-5p, miR-424-5p, miR-495-3p, and miR-92a-3p. For one of the miRNAs—miR-29c-3p—the association with the ER(+)/PgR(−) phenotype was confirmed in the TCGA cohort (p-value = 0.024; T-test). HER2 amplification/overexpression in the NanoString cohort was related to significant differences observed in 33 miRNA expression levels (FDR ≤ 0.2; ANOVA). The association with HER2 status was confirmed in the TCGA cohort for four miRNAs (miR-1180-3p, miR-223-3p, miR-30d-5p, and miR-195-5p). The main differences in miRNA expression amongst single hormone receptor-positive tumors were identified according to their HER2 status. However, ER(+)/PgR(−) cases tended to express higher levels of miRNAs associated with ER-positivity (miR-30a-5p, miR-29c-3p, miR-141-3p), whereas ER(−)/PgR(+) cancers showed elevated levels of miRNAs characteristic for double- and triple-negative tumors (miR-92a-3p, miR-424-5p). Further studies are necessary to comprehensively analyze miRNA signatures characteristic of ER(−)/PgR(+) and ER(+)/PgR(−) tumors.

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Section: Discussionsupporting

confidence: 87%

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers Is Mainly Dependent on HER2 Status—A Pilot Study

et al. 2020

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“…E.g. while members of the mir-181 family are up regulated in breast cancer in general, miR-181c in particular is activated by the expression of HER2 gene [25]. Also, miR-140 has been found suppressed by estrogen stimulation in ERα-positive breast cancer cells, most likely due to ER response elements in the flanking element of the miR-140 promoter [26].…”

Section: Introductionmentioning

confidence: 99%

The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer

et al. 2020

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miRNAs are an important class of small non-coding RNAs, which play a versatile role in gene regulation at the post-transcriptional level. Expression of miRNAs is often deregulated in human cancers. We analyzed small RNA massive parallel sequencing data from 50 locally advanced breast cancers aiming to identify novel breast cancer related miRNAs. We successfully predicted 10 novel miRNAs, out of which 2 (hsa-miR-nov3 and hsa-miR-nov7) were recurrent. Applying high sensitivity qPCR, we detected these two microRNAs in 206 and 214 out of 223 patients in the study from which the initial cohort of 50 samples were drawn. We found hsa-miR-nov3 and hsa-miR-nov7 both to be overexpressed in tumor versus normal breast tissue in a separate set of 13 patients (p = 0.009 and p = 0.016, respectively) from whom both tumor tissue and normal tissue were available. We observed hsa-miR-nov3 to be expressed at higher levels in ER-positive compared to ER-negative tumors (p = 0.037). Further stratifications revealed particularly low levels in the her2-like and basallike cancers compared to other subtypes (p = 0.009 and 0.040, respectively). We predicted target genes for the 2 microRNAs and identified inversely correlated genes in mRNA expression array data available from 203 out of the 223 patients. Applying the KEGG and GO annotations to target genes revealed pathways essential to cell development, communication and homeostasis. Although a weak association between high expression levels of hsa-miR-nov7 and poor survival was observed, this did not reach statistical significance. hsa-miR-nov3 expression levels had no impact on patient survival.

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“…A study investigating miR-195 as a biomarker in CRC demonstrated that the downregulation of miR-195 was associated with poor prognosis and lymph node metastasis (6). miR-195 has also been described as a biomarker in cervical cancer, osteosarcoma, adrenocortical cancer and breast cancer (21,(36)(37)(38)(39)(40). Zhao et al (38) found that miR-195 has a higher sensitivity for breast cancer detection, and the expression level of miR-195 has been found to significantly predict the survival rates of patients with HER2-positive breast cancer (36).…”

Section: Discussionmentioning

confidence: 99%

“…miR-195 has also been described as a biomarker in cervical cancer, osteosarcoma, adrenocortical cancer and breast cancer (21,(36)(37)(38)(39)(40). Zhao et al (38) found that miR-195 has a higher sensitivity for breast cancer detection, and the expression level of miR-195 has been found to significantly predict the survival rates of patients with HER2-positive breast cancer (36). Zhang et al (37) reported that use of a serum miRNA panel, comprising miR-16-2*, miR-195, miR-2861 and miR-497, was able to distinguish cervical cancer from cervical intraepithelial neoplasia and healthy controls with high accuracy.…”

Section: Discussionmentioning

confidence: 99%

Identification of miR-195-3p as an oncogene in RCC

Jin¹,

Li²,

Li³

et al. 2017

Molecular Medicine Reports

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There is increasing evidence that the deregulation of microRNAs (miRNAs; miRs) contributes to tumorigenesis. Previous studies have shown that miR‑195 is downregulated in various types of cancer. The present study aimed to investigate the function and expression levels of miR‑125b. Results of qPCR revealed that miR‑195‑3p, the mature sequence of miR‑195, was upregulated in renal cell carcinoma (RCC) tissues and cell lines (786‑O, 769P and ACHN). This indicated that the function and role of miR‑195‑3p may differ in different types of tumor. To assess the function of miR‑195‑3p in RCC cell lines, cell proliferation was examined using MTT and CCK‑8 assays, mobility was assessed using a cell scratch assay, Transwell migration assay and invasion assay, and apoptosis was examined using flow cytometry. These assessments were also performed in cells with upregulated or downregulated miR‑195‑3p via transfection with synthesized miR‑195‑3p mimic or inhibitor. The results revealed that the overexpression of miR‑195‑3p promoted 786‑O and ACHN RCC cell proliferation, migration and invasion, and inhibited cell apoptosis, whereas the downregulation of miR‑195‑3p suppressed cell proliferation, migration and invasion, and induced cell apoptosis. These results indicated that miR‑195‑3p was associated with the tumorigenesis of RCC, with further investigations to focus on the pathway and use of miR‑195‑3p as a clinical biomarker for RCC.

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Identification of new miRNA biomarkers associated with HER2-positive breast cancers

Cited by 20 publications

References 27 publications

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers Is Mainly Dependent on HER2 Status—A Pilot Study

microRNA Expression Profile in Single Hormone Receptor-Positive Breast Cancers Is Mainly Dependent on HER2 Status—A Pilot Study

The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer

Identification of miR-195-3p as an oncogene in RCC

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