Cancer Biomarkers - Volume 30, issue 4

Authors: Tan, Huiping | Wu, Chunlin | Huang, Bo | Jin, Lei | Jiang, Xiangbing

Article Type: Research Article

Abstract: As a result of metastasis and high recurrence, ovarian carcinoma (OC) is one of the most frequent gynecological carcinomas affecting women up to now. In spite of advances in OC treatments, the molecular mechanisms underlying OC progression are still needed to be deeply understood. MicroRNAs (miRNAs) with aberrant expressions are widely known to regulate target genes so as to mediate diverse biological activities of tumor cells. In the present study, we inspected the expression profile and latent mechanism of miR-3666 in OC. First of all, our research revealed the down-regulated miR-3666 in OC cells. Furthermore, miR-3666 up-regulation could repress cell …proliferation and migration as well as induce cell apoptosis in OC. In addition, we unmasked that miR-3666 targeted STAT3 (signal transducer and activator of transcription 3) and further down-regulated STAT3 expression. Moreover, adenylate kinase 4 (AK4) was transcriptionally enhanced by STAT3, and then miR-3666 restrained AK4 expression by mediating STAT3. In the end, rescue experiments depicted that miR-3666 suppressed the development of OC via STAT3-mediated AK4. We uncovered that miR-3666 inhibited the tumorigenesis and even development of OC via suppressing STAT3/AK4 axis, offering a novel biomarker and therapeutic target for OC. Show more

Keywords: Ovarian carcinoma (OC), miR-3666, STAT3, AK4

DOI: 10.3233/CBM-190538

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 355-363, 2021

Authors: Sanchez-Lopez, Jose Manuel | Mandujano-Tinoco, Edna Ayerim | Garcia-Venzor, Alfredo | Lozada-Rodriguez, Laura Fatima | Zampedri, Cecilia | Uribe-Carvajal, Salvador | Melendez-Zajgla, Jorge | Maldonado, Vilma | Lizarraga, Floria

Article Type: Research Article

Abstract: BACKGROUND: Long-non-coding RNAs, a class of transcripts with lengths > 200 nt, play key roles in tumour progression. Previous reports revealed that LINC00052 (long intergenic non-coding RNA 00052) was strongly downregulated during breast cancer multicellular spheroids formation and suggested a role in cell migration and oxidative metabolism. OBJECTIVE: To examine the function of LINC00052 in MCF-7 breast cancer cells. METHODS: Loss-of-function studies were performed to evaluate LINC00052 role on MCF-7 breast cancer cells. Microarray expression assays were performed to determine genes and cellular functions modified after LINC00052 knockdown. Next, the impact …of LINC00052 depletion on MCF-7 cell respiration and migration was evaluated. RESULTS: 1,081 genes were differentially expressed upon LINC00052 inhibition. Gene set enrichment analysis, Gene Ontology and Key Pathway Advisor analysis showed that signalling networks related to cell migration and oxidative phosphorylation were enriched. However, whereas LINC00052 knockdown in MCF-7 cells revealed marginal difference in oxygen consumption rates when compared with control cells, LINC00052 inhibition enhanced cell migration in vitro and in vivo , as observed using a Zebrafish embryo xenotransplant model. CONCLUSION: Our data show that LINC00052 modulates MCF-7 cell migration. Genome-wide microarray experiments suggest that cancer cell migration is affected by LINC00052 through cytoskeleton modulation and Notch/β -catenin/NF-κ B signalling pathways. Show more

Keywords: LINC00052, cell migration, transcriptome analysis, breast cancer

DOI: 10.3233/CBM-200337

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 365-379, 2021

Authors: Tölle, Angelika | Jung, Klaus | Friedersdorff, Frank | Maxeiner, Andreas | Lein, Michael | Fendler, Annika | Stephan, Carsten

Article Type: Research Article

Abstract: BACKGROUND: There is an urgent need for better prostate cancer (PCa) biomarkers due to the low specificity of prostate specific antigen (PSA). OBJECTIVE: Prostate Health Index (PHI) is an advanced PSA-based test for early detection of PCa. The present study aim was to investigate the potential improvement of diagnostic accuracy of PHI by its combination with suitable discriminative microRNAs (miRNAs). METHODS: A two-phase study was performed. In a discovery phase, a panel of 177 miRNAs was measured in ten men with biopsy proven PCa and ten men with histologically no evidence of malignancy …(NEM). These results were validated in a second phase including 25 patients in each group. The patients of all groups were matched regarding their PSA values and PHI were measured. RESULTS: Based on data in the discovery phase, four elevated miRNAs were selected as potential miRNA candidates for further validation. A combination of miR-222-3p as the best discriminative miRNA with PHI extended the diagnostic accuracy of PHI from an AUC value of 0.690 to 0.787 and resulted in a sensitivity of 72.0% and a specificity of 84.0%. CONCLUSION: Circulating microRNAs show useful diagnostic potential in combination with common used biomarkers to enhance their diagnostic power. Show more

Keywords: Prostate cancer, PHI, diagnosis, miRNA, prediction

DOI: 10.3233/CBM-201600

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 381-393, 2021

Authors: Zheng, Hailun | Zhang, Mei | Ke, Xiquan | Deng, Xiaojing | Li, Dapeng | Wang, Qizhi | Yan, Shanjun | Xue, Yongju | Wang, Qiangwu

Article Type: Research Article

Abstract: BACKGROUND: Glycolysis was an essential driver of chemo-resistance in colorectal cancer (CRC), albeit with limited molecular explanations. OBJECTIVE: We strived to elucidate the involvement of lncRNA XIST/miR-137/PKM axis in chemo-tolerance and glycolysis of CRC. METHODS: Altogether 212 pairs of tumor tissues and adjacent normal tissues were collected from CRC patients. Moreover, human CRC epithelial cell lines, including HT29, SW480, SW620 and LoVo, were purchased in advance, and their activity was estimated after transfection of si-XIST or miR-137 mimic. Furthermore, 5-FU/cisplatin-resistance of CRC cells was determined through MTT assay, and glycolytic potential of …CRC cells was appraised based on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). RESULTS: Highly-expressed XIST were predictive of severe symptoms and unfavorable 3-year survival of CRC patients (P < 0.05). Besides, silencing of XIST not only diminished proliferative, migratory and invasive power of CRC cells (P < 0.05), but also enhanced sensitivity of CRC cells responding to 5-FU/cisplatin (P < 0.05). Glycolytic potency of CRC cells was also undermined by si-XIST, with decreased maximal respiration and maximal glycolytic capacity in the si-XIST group as relative to NC group (P < 0.05). Nevertheless, miR-137 mimic attenuated the facilitating effect of pcDNA3.1-XIST on proliferation, migration, invasion, 5-FU/cisplatin-resistance and glycolysis of CRC cells (P < 0.05). Ultimately, ratio of PKM2 mRNA and PKM1 mRNA, despite being up-regulated by pcDNA3.1-XIST, was markedly lowered when miR-137 mimic was co-transfected (P < 0.05). CONCLUSIONS: LncRNA XIST/miR-137 axis reinforced glycolysis and chemo-tolerance of CRC by elevating PKM2/PKM1 ratio, providing an alternative to boost chemo-therapeutic efficacy of CRC patients. Show more

Keywords: LncRNA XIST, miR-137, colorectal cancer, glycolysis, chemo-resistance, cell migration, cell invasion

DOI: 10.3233/CBM-201740

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 395-406, 2021

Authors: Wang, Jie | You, Jialing | Gong, Ding | Xu, Ying | Yang, Bo | Jiang, Canhua

Article Type: Research Article

Abstract: OBJECTIVE: To explore the pathogenesis of oral submucosal fibrosis (OSF) by analyzing the impact of Platelet Derived Growth Factor (PDGF)-BB on oral mucosal fibroblasts (FB) and PDGFR-β /Phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT) signaling pathway. METHODS: The isolated and purified oral mucosal fibroblasts were divided into four groups: the control group (CON, 10% FBS DMEM), the PDGF-BB group (40 ng/ml PDGF-BB), the PDGF-BB+IMA group (40 ng/ml PDGF-BB and 60 μ mol/L IMA), and the PDGF-BB+LY294002 group (40 ng/ml PDGF-BB and 48 μ mol/L LY294002). Primary human FB cells were isolated …and cultured for detecting the effects of PDGF-BB on α -smooth muscle actin (α -SMA) by indirect immunofluorescence. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) method and scratch test were used to detect the proliferation and migration of FB. Western blots were used to detect the synthesis of type I collagen (Col I) and the expression of PDGFR-β /PI3K/AKT signaling pathway-related proteins. The effects of PDGFR-β inhibitor and PI3K inhibitor were observed. RESULTS: Compared with group CON, group IMA, and group LY294002, α -SMA was upregulated in group PDGF-BB (p < 0.05), with higher OD490 nm value (p < 0.05), narrower average scratch width, and higher relative cell migration rate (p < 0.05). The expression levels of Col I, p-PDGFR-β , p-PI3K, and p-AKT were higher in group PDGF-BB (p < 0.05). CONCLUSIONS: PDGF-BB induces FB to transform into myofibroblasts (MFB) through the PDGFR-β /PI3K/AKT signaling pathway, and promotes the proliferation, migration, and collagen synthesis. Show more

Keywords: PDGF-BB, oral mucosal fibroblasts, myofibroblasts, biological behavior, signaling pathway

DOI: 10.3233/CBM-201681

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 407-415, 2021

Authors: Li, Huayao | Gao, Chundi | Zhuang, Jing | Liu, Lijuan | Yang, Jing | Liu, Cun | Zhou, Chao | Feng, Fubin | Liu, Ruijuan | Sun, Changgang

Article Type: Research Article

Abstract: BACKGROUND: Invasive breast cancer is a highly heterogeneous tumor, although there have been many prediction methods for invasive breast cancer risk prediction, the prediction effect is not satisfactory. There is an urgent need to develop a more accurate method to predict the prognosis of patients with invasive breast cancer. OBJECTIVE: To identify potential mRNAs and construct risk prediction models for invasive breast cancer based on bioinformatics METHODS: In this study, we investigated the differences in mRNA expression profiles between invasive breast cancer and normal breast samples, and constructed a risk model for the …prediction of prognosis of invasive breast cancer with univariate and multivariate Cox analyses. RESULTS: We constructed a risk model comprising 8 mRNAs (PAX7 , ZIC2, APOA5, TP53AIP1, MYBPH, USP41, DACT2, and POU3F2 ) for the prediction of invasive breast cancer prognosis. We used the 8-mRNA risk prediction model to divide 1076 samples into high-risk groups and low-risk groups, the Kaplan-Meier curve showed that the high-risk group was closely related to the poor prognosis of overall survival in patients with invasive breast cancer. The receiver operating characteristic curve revealed an area under the curve of 0.773 for the 8 mRNA model at 3-year overall survival, indicating that this model showed good specificity and sensitivity for prediction of prognosis of invasive breast cancer. CONCLUSIONS: The study provides an effective bioinformatic analysis for the better understanding of the molecular pathogenesis and prognosis risk assessment of invasive breast cancer. Show more

Keywords: Invasive breast cancer, univariate and multivariate Cox analyses, bioinformatic analysis, 8-mRNA model

DOI: 10.3233/CBM-201684

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 417-428, 2021

Authors: Espinosa, Magali | Lizárraga, Floria | Vázquez-Santillán, Karla | Hidalgo-Miranda, Alfredo | Piña-Sánchez, Patricia | Torres, Javier | García-Ramírez, Román A. | Maldonado, Vilma | Melendez-Zajgla, Jorge | Ceballos-Cancino, Gisela

Article Type: Research Article

Abstract: BACKGROUND: Smac/DIABLO is a proapoptotic protein deregulated in breast cancer, with a controversial role as a tumor marker, possibly due to a lack of correlative mRNA and protein analyses. OBJECTIVE: To investigate the association of Smac/DIABLO gene and protein levels with clinical variables in breast cancer patients. METHODS: Smac/DIABLO mRNA expression was analyzed by qPCR in 57 frozen tissues, whereas protein levels were assessed by immunohistochemistry in 82 paraffin-embedded tissues. Survivin mRNA levels were also measured. In vitro assays were performed to investigate possible regulators of Smac/DIABLO. RESULTS: Higher …levels of Smac/DIABLO mRNA and protein were found in estrogen receptor (ER)-positive samples (p = 0.0054 and p = 0.0043, respectively) in comparison to ER-negative tumors. A negligible positive association was found between Smac/DIABLO and survivin expression. In vitro assays showed that Smac/DIABLO is not regulated by ER and, conversely, it does not participate in ER expression modulation. CONCLUSIONS: mRNA and protein levels of Smac/DIABLO were increased in ER-positive breast tumors in comparison with ER-negative samples, although the mechanism of this regulation is still unknown. Public databases showed a possible clinical relevance for this association. Show more

Keywords: Smac/DIABLO, survivin, breast cancer, estrogen receptor

DOI: 10.3233/CBM-200535

Citation: Cancer Biomarkers, vol. 30, no. 4, pp. 429-446, 2021