Pancreatic cancer is the most lethal malignancy of the gastrointestinal tract. Due to its propensity for early local and distant spread, affected patients possess extremely poor prognosis. Currently applied treatments are not effective enough to eradicate all cancer cells, and minimize their migration. Besides, these treatments are associated with adverse effects on normal cells and organs. These therapies are not able to increase the overall survival rate of patients; hence, finding novel adjuvants or alternatives is so essential. Up to now, medicinal herbs were utilized for therapeutic goals. Herbal-based medicine, as traditional biotherapeutics, were employed for cancer treatment. Of them, apigenin, as a bioactive flavonoid that possesses numerous biological properties (e.g., anti-inflammatory and anti-oxidant effects), has shown substantial anticancer activity. It seems that apigenin is capable of suppressing the proliferation of cancer cells via the induction of cell cycle arrest and apoptosis. Besides, apigenin inhibits metastasis via down-regulation of matrix metalloproteinases and the Akt signaling pathway. In pancreatic cancer cells, apigenin sensitizes cells in chemotherapy, and affects molecular pathways such as the hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1). Herein, the biotherapeutic activity of apigenin and its mechanisms toward cancer cells are presented in the current review to shed some light on anti-tumor activity of apigenin in different cancers, with an emphasis on pancreatic cancer.

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: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the tumor microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer-associated fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-derived exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental factors such as CAFs, and the associated derived exosomes.

: DNA damage usually happens in all cell types, which may originate from endogenous sources, (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to large structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. DNA repair, as the most significant response to DNA damage, provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes are serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered as a crucial factor in the carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss about the potential promises of these mechanisms in finding new targets for the treatment of cancer.

Background Breast cancer (BC) is the most invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered critical nutrition that many cancer cells, particularly BC cells, are dependent on it for growth and proliferation. Therefore, targeting glutamine metabolism, especially enzymes that are related to this pathway, can be beneficial to design anti-cancer agents. Recent evidence has shown that microRNAs (miRNAs), with a short length and single-strand properties, play a prominent role in regulating the genes related to glutamine metabolism, which may control the development of cancer. Methods In silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism. The expression level of these two miRNAs was evaluated in eighty BC tissues and normal adjacent tissues. Furthermore, GSE38167, GSE38867, GSE42128, GSE45666, and GSE53179 were employed from gene expression omnibus (GEO). The Limma package was utilized to identify differentially expressed miRNAs (DEMs) of mentioned datasets to evaluate miR-513c and miR-3163 expression. Further, in silico analysis was utilized to predict the potential biological processes and molecular pathways of miR-513c and miR-3163, based on their target genes. Results In silico studies revealed top categories of biological processes and cellular pathways that might play a critical role in metabolism reprogramming and cancer development and were target genes for miR-513c and miR-3163. The current study showed that miR-513c (p value = 0.02062 and FC =  − 2.3801) and miR-3163 (p value = 0.02034 and FC =  − 2.3792) were downregulated in tumor tissues compared to normal adjacent tissues. The analysis of GEO microarray datasets showed that miR-513c was downregulated in GSE38167, GSE38867, GSE42128, GSE45666 and GSE53179, whereas there was a significant downregulation of miR-3163 in only two studies, including GSE38867 and GSE42128 that they were in accordance with our experimental results. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history of cancer, and abortion history. Conclusion MiR-513c and miR-3163 were downregulated in BC tissues, which might serve as tumor suppressors. They are suggested as potential therapeutic targets for patients with BC.

Background: Breast cancer (BC) is the most common malignancy among women with a high mortality rate. The blockade of asparagine-related pathways may be an effective measurement to control the progression and reduction of BC metastasis potential. Recently, it has been shown that various miRNAs, as part of small non-coding RNAs, have a great role in cancer development, especially asparagine-related pathways, to modulate the invasiveness. Objective: This study aimed to evaluate the expression of miR-130a-5p and miR-615-3p in tumoral and non-tumoral adjacent tissues of patients with BC. Methods: There is a chance that asparagine metabolism is influenced by miR-130a-5p and miR-615-3p confirmed by bioinformatics analysis. Hence, real-time PCR was conducted on eighty BC tumoral and non-tumoral adjacent tissues to evaluate the expression level of the two miRNAs. To predict the potential biological process and molecular pathways of miR-130a-5p, in-silico analysis was performed. Results: This study indicated that miR-130a was downregulated in tumoral tissues compared to non-tumoral adjacent tissues (P-value= 0.01443 and fold change= -2.5137), while miR-615-3p did not show a significant difference between the two groups. Furthermore, the subgroup studies did not reveal any significant correlation between the expression of these two miRNAs and subfactors. Furthermore, insilico studies unraveled several biological processes related to amino-acid metabolism, as well as pathways related to tumor development such as Phosphatase and Tensin Homolog (PTEN) and JAK-STAT pathways among miR-130a-5p target genes. Conclusion: Our findings indicate that miRNA-130a-5p is downregulated in BC tissues and may play a tumor suppressor role in patients with BC. Therefore, it may be suggested as a potential diagnostic and therapeutic target for BC.

: Cisplatin has a broad-spectrum antitumor activity and is widely used for the treatment of various malignant tumors. However, acquired or intrinsic resistance of cisplatin is a major problem for patients during the therapy. Recently, it has been reported cancer stem cell (CSC)-derived drug resistance is a great challenge of tumor development and recurrence; therefore, the sensitivity of breast cancer stem cells (BCSCs) to cisplatin is of particular importance. Increasing evidence has shown that there is a relationship between cisplatin resistance/sensitivity genes and related miRNAs. It is known that dysregulation of relevant miRNAs plays a critical role in regulating target genes of cisplatin resistance/sensitivity in various pathways such as cellular uptake/efflux, Epithelial-Mesenchymal Transition (EMT), hypoxia, and apoptosis. Furthermore, the efficacy of the current chemotherapeutic drugs, including cisplatin for providing personalized medicine, can be improved by controlling the expression of miRNAs. Thus, potential targeting of miRNAs can lead to miRNA-based therapies, which will help overcome drug resistance and develop more effective personalized anti-cancer and co-treatment strategies in breast cancer. In this review, we summarized the general understandings of miRNA-regulated biological processes in breast cancer, particularly focused on the role of miRNA in cisplatin resistance/sensitivity.