Epigenetic regulation of autophagy by non-coding RNAs in gastrointestinal tumors: Biological functions and therapeutic perspectives.

Cancer is the manifestation of changes and mutations in genetic and epigenetic levels. Non-coding RNAs (ncRNAs) are commonly dysregulated in disease pathogenesis, and their role in cancer has been well-documented. The ncRNAs regulate various molecular pathways and mechanisms in cancer that can lead to induction/inhibition of carcinogenesis. Autophagy is a molecular "self-digestion" mechanism its function can be pro-survival or pro-death in tumor cells. The aim of the present review is to evaluate the role of ncRNAs in regulating autophagy in gastrointestinal tumors. The role of the ncRNA/autophagy axis in affecting the progression of gastric, liver, colorectal, pancreatic, esophageal, and gallbladder cancers is investigated. Both ncRNAs and autophagy mechanisms can function as oncogenic or onco-suppressor and this interaction can determine the growth, invasion, and therapy response of gastrointestinal tumors. ncRNA/autophagy axis can reduce/increase the proliferation of gastrointestinal tumors via the glycolysis mechanism. Furthermore, related molecular pathways of metastasis, such as EMT and MMPs, are affected by the ncRNA/autophagy axis. The response of gastrointestinal tumors to chemotherapy and radiotherapy can be suppressed by pro-survival autophagy, and ncRNAs are essential regulators of this mechanism. miRNAs can regulate related genes and proteins of autophagy, such as ATGs and Beclin-1. Furthermore, lncRNAs and circRNAs down-regulate miRNA expression via sponging to modulate the autophagy mechanism. Moreover, anti-cancer agents can affect the expression level of ncRNAs regulating autophagy in gastrointestinal tumors. Therefore, translating these findings into clinics can improve the prognosis of patients.

Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges.

Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt signaling contributes to proliferation, invasion, and inhibition of apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions with high prevalence of viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, and inflammation can also lead to initiation and development of HCC. The treatment of HCC depends on the identification of oncogenic factors that lead tumor cells to develop resistance to therapy. The present review article focuses on the role of PI3K/Akt signaling in HCC progression. Activation of PI3K/Akt signaling promotes glucose uptake, favors glycolysis and increases tumor cell proliferation. It inhibits both apoptosis and autophagy while promoting HCC cell survival. PI3K/Akt stimulates epithelial-to-mesenchymal transition (EMT) and increases matrix-metalloproteinase (MMP) expression during HCC metastasis. In addition to increasing colony formation capacity and facilitating the spread of tumor cells, PI3K/Akt signaling stimulates angiogenesis. Therefore, silencing PI3K/Akt signaling prevents aggressive HCC cell behavior. Activation of PI3K/Akt signaling can confer drug resistance, particularly to sorafenib, and decreases the radio-sensitivity of HCC cells. Anti-cancer agents, like phytochemicals and small molecules can suppress PI3K/Akt signaling by limiting HCC progression. Being upregulated in tumor tissues and clinical samples, PI3K/Akt can also be used as a biomarker to predict patients' response to therapy.

Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action.

Breast cancer (BC) is one of the most common cancers in females and is responsible for the highest cancer-related deaths following lung cancer. The complex tumor microenvironment and the aggressive behavior, heterogenous nature, high proliferation rate, and ability to resist treatment are the most well-known features of BC. Accordingly, it is critical to find an effective therapeutic agent to overcome these deleterious features of BC. Resveratrol (RES) is a polyphenol and can be found in common foods, such as pistachios, peanuts, bilberries, blueberries, and grapes. It has been used as a therapeutic agent for various diseases, such as diabetes, cardiovascular diseases, inflammation, and cancer. The anticancer mechanisms of RES in regard to breast cancer include the inhibition of cell proliferation, and reduction of cell viability, invasion, and metastasis. In addition, the synergistic effects of RES in combination with other chemotherapeutic agents, such as docetaxel, paclitaxel, cisplatin, and/or doxorubicin may contribute to enhancing the anticancer properties of RES on BC cells. Although, it demonstrates promising therapeutic features, the low water solubility of RES limits its use, suggesting the use of delivery systems to improve its bioavailability. Several types of nano drug delivery systems have therefore been introduced as good candidates for RES delivery. Due to RES's promising potential as a chemopreventive and chemotherapeutic agent for BC, this review aims to explore the anticancer mechanisms of RES using the most up to date research and addresses the effects of using nanomaterials as delivery systems to improve the anticancer properties of RES.

Impacts of opium addiction on patterns of angiographic findings in patients with acute coronary syndrome.

Opium is one of the most abused substances in the Middle East. The effects of opium use on coronary artery disease (CAD) are a matter of debate. This study aimed to assess the association between opium use and angiographic findings as well as the complexity of CAD in patients with acute coronary syndrome (ACS) diagnosis. In this case-control study, all patients admitted for coronary angiography from 2019 to 2020 were evaluated. After applying the eligibility criteria, they were categorized into two groups opium and non-opium based on their history of opium use. Both groups were matched regarding the demographic features. The prevalence, location, and severity of obstruction of the vessels were compared between the non-opium and opium groups. The SYNTAX score was also calculated and compared between the two groups. The scores ≤ 22 are considered low risk and the higher scores are a non-low risk. P value < 0.05 is considered significant. A total of 170 patients with a mean age of 61.59 ± 9.07 years were finally enrolled in our study. Regarding the severity of vascular involvement, there was a significant difference between the non-opium and opium groups in LAD (P = 0.025), and PLV (P = 0.018) vessels. From the location points of view of obstructive coronary artery involved segments, only in the PDA (P = 0.006), and LCX (P = 0.004) vessels, a significant difference was observed. Moreover, 47.1% of opium and 30.6% of non-opium use group were in the non-low risk SYNTAX score classification which is a statistically significant difference between these two groups (P value = 0.048). Opium, as an independent risk factor for cardiovascular diseases, can have specific effects on angiographic findings in patients with acute coronary syndrome. Likewise, the complexity of CAD in opium users who undergo percutaneous coronary intervention is significantly higher.

Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play pivotal roles in proliferation, apoptosis, migration, and invasion of renal cell carcinoma (RCC) cells. This study is aimed to systematically summarize the current evidence regarding the clinical implications of circRNAs in RCC patients. METHODS: A systematic search in PubMed, Embase, and Web of Science was performed until January 1, 2022. The correlation between the expression of circRNAs and clinicopathological, prognostic, and diagnostic features of RCC was evaluated using the meta-analysis. RESULTS: Ultimately, 41 studies with 3485 RCC patients were included in this study: 26 studies for clinicopathological features, 31 studies for prognosis, and eight studies for diagnosis. Altered expression of circRNAs was significantly associated with clinicopathological characteristics of RCC, including tumor size, tumor stage, lymph node metastasis, distant metastasis, and TNM stage. The tumor promoter circRNAs were associated with reduced overall survival (OS) (Hazard Ratio (HR) = 1.98, 95% confidence interval [CI] 1.68-2.34) and disease/progression/recurrence-free survival (DFS/PFS/RFS) (HR = 2.34, 95% CI 1.85-2.97). Contrarily, the tumor suppressor circRNAs were linked with better OS (HR = 0.49, 95% CI 0.40-0.60) and DFS/PFS/RFS (HR = 0.40, 95% CI 0.28-0.59). The pooled sensitivity and specificity of circRNAs for RCC diagnosis in tissue samples were both 0.84. These results in fluid samples (serum and urine) were 0.78 and 0.69, respectively. CONCLUSION: CircRNAs can serve as promising diagnostic and prognostic biomarkers for RCC.

Circular RNA MYLK as a prognostic biomarker in patients with cancers: A systematic review and meta-analysis.

BACKGROUND: Circular RNA (circRNA) myosin light chain kinase (circMYLK) has recently received increasing attention in cancer biology. Several studies have suggested that circMYLK expression is linked to prognosis and clinicopathological characteristics of various malignancies. AIMS: This study was carried out to systematically review the impact of circMYLK on the progression of multiple cancers and assess the significance of circMYLK in the prognosis and clinicopathological features of the patients. METHODS: PubMed, Web of Science, and Embase were systematically searched until July 2, 2021. For qualitative synthesis, the signaling pathways of circMYLK in the progression of different cancers were summarized. Regarding the meta-analysis, overall survival (OS) and eight clinicopathological characteristics of patients with cancers were addressed. Odds ratios (ORs) and hazard ratios (HRs) were calculated to assess the association of circMYLK with prognostic and clinicopathological features. RESULTS: Twelve studies investigating the role of circMYLK in cancer progression met the inclusion criteria. Among these, seven studies investigated the prognostic significance of circMYLK, and nine studies ascertained the clinicopathological importance of circMYLK in patients with various malignancies. CircMYLK acts as a tumor promoter circRNA, leading to migration, proliferation, invasion, and metastasis of neoplastic cells and inhibiting their apoptosis through interaction with several miRNAs and corresponding downstream signaling pathways. Overexpression of circMYLK was correlated with poor OS (HR = 1.75; 95% confidence interval [CI] 1.52-2.02) and larger tumor size (OR = 2.90; 95% CI 1.03-8.15), higher T stage (OR = 2.49; 95% CI 1.20-5.18), lymph node metastasis (OR = 2.55; 95% CI 1.41-4.62), and higher TNM stage (OR = 4.62; 95% CI 2.99-7.14). CONCLUSIONS: CircMYLK is involved in the progression of numerous cancers via different signaling pathways. This circRNA can serve as a promising prognostic biomarker for several types of malignancies. Furthermore, high expression of circMYLK is associated with advanced clinicopathological characteristics in various tumors.

The tangled web of dyslipidemia and cancer: Is there any association?

Cancer is a primary cause of mortality around the world and imposes a significant physiological, psychological, and financial burden on patients. Lipids regulate cell cycle progression and affect cell proliferation, migration, and apoptosis. Therefore, alterations in serum lipid levels might contribute to carcinogenesis. In this article, we review the relationships between triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels and different types of cancer. Then, we examine the association between cancer and familial hypercholesterolemia. Finally, we evaluate the impact of statins on different types of cancer. Increased total cholesterol has been reported to increase cellular proliferation and angiogenesis in tumors and inhibit apoptosis. Increased LDL-C has been reported to induce inflammation and increase susceptibility to oxidative damage. HDL-C has anti-oxidation, anti-inflammatory, and antiproliferative properties. Increased levels of serum TG can induce oxidative stress and a chronic inflammatory state and therefore contribute to the proliferation and progression of cancer cells. Statins decrease downstream products of cholesterol synthesis that are crucial in cell proliferation and growth. Thus, lipid components can have prognostic value in cancer and management of serum lipid levels through lifestyle changes and medical therapy can be beneficial in cancer prevention and treatment.