The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis.

Background: Bronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. Methods: This study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. Results: The current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

Computer-assisted drug discovery (CADD) of an anti-cancer derivative of the theobromine alkaloid inhibiting VEGFR-2.

VEGFR-2 is a significant target in cancer treatment, inhibiting angiogenesis and impeding tumor growth. Utilizing the essential pharmacophoric structural properties, a new semi-synthetic theobromine analogue (T-1-MBHEPA) was designed as VEGFR-2 inhibitor. Firstly, T-1-MBHEPA's stability and reactivity were indicated through several DFT computations. Additionally, molecular docking, MD simulations, MM-GPSA, PLIP, and essential dynamics (ED) experiments suggested T-1-MBHEPA's strong binding capabilities to VEGFR-2. Its computational ADMET profiles were also studied before the semi-synthesis and indicated a good degree of drug-likeness. T-1-MBHEPA was then semi-synthesized to evaluate the design and the in silico findings. It was found that, T-1-MBHEPA inhibited VEGFR-2 with an IC50 value of 0.121 ± 0.051 µM, as compared to sorafenib which had an IC50 value of 0.056 µM. Similarly, T-1-MBHEPA inhibited the proliferation of HepG2 and MCF7 cell lines with IC50 values of 4.61 and 4.85 µg/mL respectively - comparing sorafenib's IC50 values which were 2.24 µg/mL and 3.17 µg/mL respectively. Interestingly, T-1-MBHEPA revealed a noteworthy IC50 value of 80.0 µM against the normal cell lines exhibiting exceptionally high selectivity indexes (SI) of 17.4 and 16. 5 against the examined cell lines, respectively. T-1-MBHEPA increased the percentage of apoptotic MCF7 cells in early and late stages, respectively, from 0.71 % to 7.22 % and from 0.13 % to 2.72 %, while the necrosis percentage was increased to 11.41 %, in comparison to 2.22 % in control cells. Furthermore, T-1-MBHEPA reduced the production of pro-inflammatory cytokines TNF-α and IL-2 in the treated MCF7 cells by 33 % and 58 %, respectively indicating an additional anti-angiogenic mechanism. Also, T-1-MBHEPA decreased significantly the potentialities of MCF7 cells to heal and migrate from 65.9 % to 7.4 %. Finally, T-1-MBHEPA's oral treatment didn't show toxicity on the liver function (ALT and AST) and the kidney function (creatinine and urea) levels of mice.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

Clinical significance of vit D and AMH and its correlation with polycystic ovarian parameters in obese and non-obese Egyptian women.

Women of reproductive age are frequently affected by the heterogeneous endocrine-metabolic conditions recognized as polycystic ovarian syndrome (PCOS). Moreover, FSH (Follicle-stimulating hormone), steroidogenesis, and LH (Luteinizing Hormone) are suppressed by the anti-Mullerian hormone, a good indicator of ovarian reserve, that is generated from granulosa cells. In the past ten years, vitamin D (VD) has attracted and maintained great interest in human health and biomedical research, particularly those about female reproductive-metabolic problems. Therefore, this study was designed to evaluate the correlation of VD and AMH with PCOS parameters in Egyptian women. Assessments were done on 35 control women and 45 PCOS sufferers. Utilizing the updated Rotterdam criteria, PCOS was identified. After recording anthropometric data, fasting serum levels of VD, follistatin (FST), insulin, FSH, LH, total testosterone (TT), sex hormone binding globulin (SHBG), as well as fasting plasma glucose (FPG), and the free androgen index (FAI) were measured in both groups. Compared to the control group, the PCOS group had a greater prevalence of hypovitaminosis D but serum levels of follistatin, LH, TT, AMH, insulin, and FPG, were considerably higher. Besides, there was a substantial inverse relationship between VD and the levels of follistatin, FPG, LH, TT, and AMH and a positive correlation with FSH in PCOS women's blood. This study revealed that hypovitaminosis D, elevated AMH, and FST may be regarded as alarming risk factors for PCOS in Egyptian women.

Rumex vesicarius L. boosts the effectiveness of sorafenib in triple-negative breast cancer by downregulating BCl2, mTOR, and JNK, and upregulating p21 expression.

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) is characterized by poor prognosis, rapid progression, serious clinical behavior, an elevated risk of metastasis, and resistance to standard treatments. Traditional medicine practitioners value Rumex vesicarius L. (RMV) for a variety of reasons, including the plant's antioxidant capabilities. Our study's goals were to ascertain the efficacy of RMV alone and in combination with sorafenib (SOR) against the aggressive TNBC cell line (MDA-MB-231) and use in vitro and in silico analysis to deduce the fundamental mechanism of action. METHODS: In the current study, molecular operating environment (MOE, 2019.0102) software was used for performing molecular docking. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to determine the cytotoxicity of RMV, SOR or RMV/SOR combination against the TNBC cell line MDA-MB-231 cells. The effects of RMV, SOR, and RMV and SOR combining on mRNAs expressions of the target genes including mTOR, p21, JNK, and BCl2 were evaluated. In TNBC cells, the relative expressions of mRNAs of the genes were examined by using real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In our experiments, we discovered that both RMV extracts alone and in combination with SOR considerably reduced cancer cell proliferation (IC50 = 0.83 and 0.19 µM, respectively). Additionally, the expression of the tumor suppressor gene p21 was elevated whereas the expression of the invasion and anti-apoptosis genes BCl2, mTOR, and JNK were significantly decreased after treatment with RMV and SOR. Based on in silico analysis, it was found that RMV extract contains bioactive chemicals with a high affinity for inhibiting JNK and VEGFR-2. CONCLUSION: In conclusion, in vitro and in silico investigations show that the RMV extract improves the anticancer efficiency of SOR through molecular processes involving the downregulation of mTOR, BCl2, and JNK1 and overexpression of p21 tumor suppressor gene. Finally, we suggest conducting additional in vivo investigations on RMV and its bioactive components to verify their potential in cancer therapy.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

New thiouracil derivatives as histone deacetylase inhibitors and apoptosis inducers: design, synthesis and anticancer evaluation.

Background: Histone deacetylase (HDAC) inhibitors have good contributions in cancer management. Aim: To introduce new active HDAC inhibitors. Methods: Design and synthesis of 16 thiouracil derivatives with deep biological and computational investigation. Results: Compounds 7a, 7c, 7d, 7e, 8a and 8f showed the highest antiproliferative effects against MCF7, HepG2 and HCT116 cell lines. Compound 7e exhibited the highest activities against HDAC1 and HDAC4. Compound 7e arrested the cell cycle of HCT116 cells at G0-G1 with significant apoptotic effect. In addition, treatment with compound 7e was associated with a significant increase in the levels of caspase-3 and caspase-8. The docking studies gave good insight about the binding patterns of the synthesized compounds against HDAC1. Conclusion: Compound 7e has a promising anticancer activity targeting HDAC.

miRNAs driving diagnosis, progression, and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.

New theobromine derivatives inhibiting VEGFR-2: design, synthesis, antiproliferative, docking and molecular dynamics simulations.

Background: VEGFR-2 is one of the most effective targets in cancer treatment. Aim: The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. Methods: In vitro and in silico evaluation of the synthesized compounds. Results: Compound 5b demonstrated excellent antiproliferative and VEGFR-2 inhibitory effects with significant apoptotic activity. It modulated the immune response by increasing IL-2 and reducing TNF-α levels. Docking and molecular dynamics simulations revealed the compound's binding affinity with VEGFR-2. Lastly, computational absorption, distribution, metabolism, excretion and toxicity studies indicated the high potential of compound 5b for drug development. Conclusion: Compound 5b could be a promising anticancer agent targeting VEGFR-2.

miRNAs orchestration of gallbladder cancer - Particular emphasis on diagnosis, progression and drug resistance.

Gallbladder cancer (GBC) is characterized by a highly invasive nature and a poor prognosis, with adenocarcinoma being the main histological subtype. According to statistical data, patients diagnosed with advanced GBC have a survival rate of less than 5% for 5 years. Despite the novel therapeutic techniques, the unsatisfactory results could be related to the underlying biology of tumor cells and resistance to chemotherapy. Early diagnosis is more important than clinical therapy as it assists in determining the pathological stage of cancer and facilitates the selection of appropriate medication. Hence, it is very important to understand the precise pathogenesis of GBC and to discover potential novel biomarkers for early diagnosis of GBC. Non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been found to influence the transcriptional regulation of target genes associated with cancer, either directly or indirectly. microRNAs are a group of small, non-coding, single-stranded RNAs that are expressed endogenously. miRNAs play significant roles in various fundamental cellular processes. Therefore, miRNAs have the potential to serve as valuable biomarkers and therapeutic targets for GBC.

Semi-synthesized anticancer theobromine derivatives targeting VEGFR-2: in silico and in vitro evaluations.

Vascular endothelial cell proliferation and angiogenesis are all crucially impacted by Endothelial Growth Factor Receptor-2 (VEGFR-2). Its expression is significantly boosted throughout pathologic angiogenesis causing the development of tumors. Sothat, inhibition of VEGFR-2 has crucial role in cancer treatment. In this study, novel semisynthetic theobromine derivatives were rationally designed as VEGFR-2 inhibitors and subjected to in vitro testing for their ability to block VEGFR-2 activation. Furthermore, the antiproliferative effects of these derivatives were evaluated. Compound 7 g exhibited the most potent anti-VEGFR-2 activity, with an IC50 value of 0.072 µM, and demonstrated excellent dose-dependent inhibitory activity against both MCF-7 and HepG2 cancer cells with IC50 values of 19.35 and 27.89 µM, respectively. Notably, compound 7 g exhibited high selectivity indices of 2.6 and 1.8 against MCF-7 and HepG2 cells, respectively. Compound 7 g induced G2/M phase cell cycle arrest, promoted apoptosis, and boosted immunomodulation by downregulating TNF-α expression and upregulating IL-2 levels in MCF-7 cells. The molecular docking analysis revealed that compound 7 g could bind effectively to the active site of VEGFR-2, and molecular dynamic simulations confirmed the stability of the VEGFR-2/compound 7 g complex. Furthermore, ADME and toxicity profiling indicated the potential suitability of these compounds as drug candidates. In summary, compound 7 g hold promise as a VEGFR-2 inhibitor.Communicated by Ramaswamy H. Sarma.

The role of miRNAs in laryngeal cancer pathogenesis and therapeutic resistance - A focus on signaling pathways interplay.

Laryngeal cancer (LC)is the malignancy of the larynx (voice box). The majority of LC are squamous cell carcinomas. Many risk factors were reported to be associated with LC as tobacco use, obesity, alcohol intake, human papillomavirus (HPV) infection, and asbestos exposure. Besides, epigenetics as non-coding nucleic acids also have a great role in LC. miRNAs are short nucleic acid molecules that can modulate multiple cellular processes by regulating the expression of their genes. Therefore, LC progression, apoptosis evasions, initiation, EMT, and angiogenesis are associated with dysregulated miRNA expressions. miRNAs also could have some vital signaling pathways such as mTOR/P-gp, Wnt/-catenin signaling, JAK/STAT, KRAS, and EGF. Besides, miRNAs also have a role in the modulation of LC response to different therapeutic modalities. In this review, we have provided a comprehensive and updated overview highlighting the microRNAs biogenesis, general biological functions, regulatory mechanisms, and signaling dysfunction in LC carcinogenesis, in addition to their clinical potential for LC diagnosis, prognosis, and chemotherapeutics response implications.

Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats.

AIM: this study aims to explore the effect of androgen receptor (AR) blockade by flutamide on some renal pathologic changes such as inflammation, apoptosis, and fibrosis in male rats. MAIN METHODS: Firstly, we investigated the potential effect of AR blockade on renal inflammatory intermediates including IL-1ß, IL-6, TNF-α, NF-Òšß proteins, and the renal gene expression of NF-Қß. Besides inflammation, we also assessed the apoptosis pathways including the caspases 3 & 9, mTOR, pAKT proteins, and BAX gene expression. Besides inflammation and apoptosis pathways, we also investigated the effect of androgen blockade on renal fibrosis intermediates including vimentin, TGFß-1, α-SMA, MMP-9, collagen type-III, collagen type-IV, and the renal expression of the col1A1 gene. Besides previous pathological pathways, we assessed the expression of chloride channel protein-5 (ClC-5), as an important regulator of many renal pathological changes. Finally, we assessed the impact of previous pathological changes on renal function at biochemical and pathological levels. KEY FINDINGS: We found that AR blockade by flutamide was associated with the down-regulation of renal inflammation, apoptosis, and fibrosis markers. It was associated with expression down-regulation of IL-1ß & IL-6, TNF-α, NF-Қß, caspases 3 & 9, mTOR, MMP-9, collagens, TGFß-1, and α-SMA. Away from down-regulation, we also found that AR blockade has upregulated ClC-5 and pAKT proteins. SIGNIFICANCE: AR is a major player in androgens-induced nephrotoxicity. AR blockade downregulates renal fibrosis, inflammation, and apoptosis pathways. It may be helpful as a strategy for alleviation of renal side effects associated with some drugs. However; this needs further investigations.

A spotlight on the interplay of signaling pathways and the role of miRNAs in osteosarcoma pathogenesis and therapeutic resistance.

Osteosarcoma (OS) is one of the most common bone cancers that constantly affects children, teenagers, and young adults. Numerous epigenetic elements, such as miRNAs, have been shown to influence OS features like progression, initiation, angiogenesis, and treatment resistance. The expression of numerous genes implicated in OS pathogenesis might be regulated by miRNAs. This effect is ascribed to miRNAs' roles in the invasion, angiogenesis, metastasis, proliferation, cell cycle, and apoptosis. Important OS-related mechanistic networks like the WNT/b-catenin signaling, PTEN/AKT/mTOR axis, and KRAS mutations are also affected by miRNAs. In addition to pathophysiology, miRNAs may influence how the OS reacts to therapies like radiotherapy and chemotherapy. With a focus on how miRNAs affect OS signaling pathways, this review seeks to show how miRNAs and OS are related.

Significance of miRNAs on the thyroid cancer progression and resistance to treatment with special attention to the role of cross-talk between signaling pathways.

Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. It has many types, the Papillary thyroid cancer (PTC)(most common and follicular thyroid carcinoma (FTC). Several risk factors have been associated with TC radiation exposure, autoimmunity, and genetics. Microribonucleic acids (miRNAs) are the most important genetic determinants of TC. They are small chains of nucleic acids that are able to inhibit the expression of several target genes. They could target several genes involved in TC proliferation, angiogenesis, apoptosis, development, and even resistance to therapy. Besides, they could influence the stemness of TC. Moreover, they could regulate several signaling pathways such as WNT/ß-catenin, PI3K/AKT/mTOR axis, JAK/STAT, TGF- ß, EGFR, and P53. Besides signaling pathways, miRNAs are also involved in the resistance of TC to major treatments such as surgery, thyroid hormone-inhibiting therapy, radioactive iodine, and adjuvant radiation. The stability and sensitivity of several miRNAs might be exploited as an approach for the usage of miRNAs as diagnostic and/or prognostic tools in TC.

miRNAs as cornerstones in adipogenesis and obesity.

In recent decades, obesity has extensively emerged to the level of pandemics. It's significantly associated with serious co-morbidities that could decrease life quality and even life expectancy. Obesity has several determinants, such as age, sex, endocrine, and genetic factors. The miRNAs have emerged as genetic factors affecting obesity. The miRNAs are small noncoding nucleic acids that can modify gene expression and hence, control biological processes. The miRNAs can greatly affect many biological processes in obesity, such as adipogenesis, lipid metabolism, and homeostasis. As a result, the entry of miRNAs in obesity therapeutic approaches has been strongly advised as miRNAs mimics, inhibitors, and stimulators. Hence, this review aims to point out a summarized and updated overview of miRNAs and their roles in obesity and its included processes, such as adipogenesis and lipid metabolism. Besides, we also review recent applications of miRNAs as a treatment approach for obesity.

Phylotypic Profiling, Distribution of Pathogenicity Island Markers, and Antimicrobial Susceptibility of Escherichia coli Isolated from Retail Chicken Meat and Humans.

Escherichia coli (E.coli) found in retail chicken meat could be causing a wide range of infections in humans and constitute a potential risk. This study aimed to evaluate 60 E. coli isolates from retail chicken meat (n = 34) and human urinary tract infections (UTIs, n = 26) for phylogenetic diversity, presence of pathogenicity island (PAI) markers, antimicrobial susceptibility phenotypes, and antimicrobial resistance genes, and to evaluate their biofilm formation capacity. In that context, confirmed E.coli isolates were subjected to phylogrouping analysis using triplex PCR, antimicrobial susceptibility testing using the Kirby-Bauer disc diffusion method; PAI distribution was investigated by using two multiplex PCRs. Most of the chicken isolates (22/34, 64.7%) were identified as commensal E. coli (A and B1), while 12 isolates (35.3%) were classified as pathogenic virulent E. coli (B2 and D). Similarly, the commensal group dominated in human isolates. Overall, 23 PAIs were detected in the chicken isolates; among them, 39.1% (9/23) were assigned to group B1, 34.8% (8/23) to group A, 4.34% (1/23) to group B2, and 21.7% (5/23) to group D. However, 25 PAIs were identified from the human isolates. PAI IV536 was the most prevalent (55.9%, 69.2%) PAI detected in both sources. In total, 37 (61.7%) isolates of the chicken and human isolates were biofilm producers. Noticeably, 100% of E. coli isolates were resistant to penicillin and rifamycin. Markedly, all E. coli isolates displayed multiple antibiotic resistance (MAR) phenotypes, and the multiple antibiotic resistance index (MARI) among E. coli isolates ranged between 0.5 and 1. Several antibiotic resistance genes (ARGs) were identified by a PCR assay; the sul2 gene was the most prevalent (38/60, 63.3%) from both sources. Interestingly, a significant positive association (r = 0.31) between biofilm production and resistance to quinolones by the qnr gene was found by the correlation analysis. These findings were suggestive of the transmission of PAI markers and antibiotic resistance genes from poultry to humans or humans to humans through the food chain. To avoid the spread of virulent and multidrug-resistant E. coli, intensive surveillance of retail chicken meat markets is required.

A review of the biological role of miRNAs in prostate cancer suppression and progression.

Prostate cancer (PC) is the third-leading cause of cancer-related deaths worldwide. Although the current treatment strategies are progressing rapidly, PC is still representing a substantial medical problem for affected patients. Several factors are involved in PC initiation, progression, and treatments failure including microRNAs (miRNAs). The miRNAs are endogenous short non-coding RNA sequence negatively regulating target mRNA expression via degradation or translation repression. miRNAs play a pivotal role in PC pathogenesis through its ability to initiate the induction of cancer stem cells (CSCs) and proliferation, as well as sustained cell cycle, evading apoptosis, invasion, angiogenesis, and metastasis. Furthermore, miRNAs regulate major molecular pathways affecting PC such as the androgen receptor (AR) pathway, p53 pathway, PTEN/PI3K/AKT pathway, and Wnt/ß-catenin pathway. Furthermore, miRNAs alter PC therapeutic response towards the androgen deprivation therapy (ADT), chemotherapy and radiation therapy (RT). Thus, the understanding and profiling of the altered miRNAs expression in PC could be utilized as a non-invasive biomarker for the early diagnosis as well as for patient sub-grouping with different prognoses for individualized treatment. Accordingly, in the current review, we summarized in updated form the roles of various oncogenic and tumor suppressor (TS) miRNAs in PC, revealing their underlying molecular mechanisms in PC initiation and progression.

MicroRNA-567 inhibits cell proliferation and induces cell apoptosis in A549 NSCLC cells by regulating cyclin-dependent kinase 8.

MicroRNA-567 (miR-567) plays a decisive role in cancers whereas its role in non-small cell lung cancer (NSCLC) is still unexplored. This study was therefore planned to explore the regulatory function of miR-567 in A549 NSCLC cells and investigate its possible molecular mechanism that may help in NSCLC treatment. In the current study, miR-567 expression was examined by quantitative real time-polymerase chain reaction (qRT-PCR) in different NSCLC cell lines in addition to normal cell line. A549 NSCLC cells were transfected by miR-567 mimic, miR-567 inhibitor, and negative control siRNA. Cell proliferation was evaluated by MTT and 5-bromo-2'deoxyuridine assays. Cell cycle distribution and apoptosis were studied by flow cytometry. Bioinformatics analysis programs were used to expect the putative target of miR-567. The expression of cyclin-dependent kinase 8 (CDK8) gene at mRNA and protein levels were evaluated by using qRT-PCR and western blotting. Our results found that miR-567 expressions decreased in all the studied NSCLC cells as compared to the normal cell line. A549 cell proliferation was suppressed by miR-567 upregulation while cell apoptosis was promoted. Also, miR-567 upregulation induced cell cycle arrest at sub-G1 and S phases. CDK8 was expected as a target gene of miR-567. MiR-567 upregulation decreased CDK8 mRNA and protein expression while the downregulation of miR-567 increased CDK8 gene expression. These findings revealed that miR-567 may be a tumor suppressor in A549 NSCLC cells through regulating CDK8 gene expression and may serve as a novel therapeutic target for NSCLC treatment.