The Role of microRNAs in Hepatocellular Cancer: A Narrative Review Focused on Tumor Microenvironment and Drug Resistance.

Globally, hepatic cancer ranks fourth in terms of cancer-related mortality and is the sixth most frequent kind of cancer. Around 80% of liver cancers are hepatocellular carcinomas (HCC), which are the leading cause of cancer death. It is well known that HCC may develop resistance to the available chemotherapy treatments very fast. One of the biggest obstacles in providing cancer patients with appropriate care is drug resistance. According to reports, more than 90% of cancer-specific fatalities are caused by treatment resistance. By binding to the 3'-untranslated region of target messenger RNAs (mRNAs), microRNAs (miRNAs), a group of noncoding RNAs which are around 17 to 25 nucleotides long, regulate target gene expression. Moreover, they play role in the control of signaling pathways, cell proliferation, and cell death. As a result, miRNAs play an important role in the microenvironment of HCC by changing immune phenotypes, hypoxic conditions, and acidification, as well as angiogenesis and extracellular matrix components. Moreover, changes in miRNA levels in HCC can effectively resist cancer cells to chemotherapy by affecting various cellular processes such as autophagy, apoptosis, and membrane transporter activity. In the current work, we narratively reviewed the role of miRNAs in HCC, with a special focus on tumor microenvironment and drug resistance.

5-Flourouracil-induced toxicity in both male and female reproductive systems: A narrative review.

The chemotherapeutic drug 5-flourouracil (5FU) is frequently used to treat a wide range of solid malignant tumors, such as colorectal, pancreatic, gastric, breast, and head and neck cancers. Its antitumoral effects are achieved by interfering with the synthesis of RNA and DNA and by inhibiting thymidylate synthase in both malignant and non-malignant cells. Therefore, it can be responsible for severe toxicities in crucial body organs, including heart, liver, kidney, and reproductive system. Given the fact that 5FU-induced reproductive toxicity may limit the clinical application of this drug, in this study, we aimed to discuss the main locations and mechanisms of the 5FU-induced reproductive toxicity. Initially, we discussed the impact of 5FU on the male reproductive system, which leads to damage of the seminiferous epithelial cells and the development of vacuoles in Sertoli cells. Although no noticeable changes occur at the histopathological level, there is a decrease in the weight of the prostate. Additionally, 5FU causes significant abnormalities in spermatogenesis, including germ cell shedding, spermatid halo formation, polynucleated giant cells, and decreased sperm count. Finally, in females, 5FU-induced reproductive toxicity is characterized by the presence of atretic secondary and antral follicles with reduced numbers of growing follicles, ovarian weight, and maturity impairment.

The Role of microRNAs in Regulating Cancer Cell Response to Oxaliplatin-Containing Regimens.

Oxaliplatin (cyclohexane-1,2-diamine; oxalate; platinum [2+]) is a third-generation chemotherapeutic drug with anticancer effects. Oxaliplatin has a role in the treatment of several cancers. It is one of the few drugs which can eliminate the neoplastic cells of colorectal cancer. Also, it has an influential role in breast cancer, lung cancer, bladder cancer, prostate cancer, and gastric cancer. Although oxaliplatin has many beneficial effects in cancer treatment, resistance to this drug is in the way to cure neoplastic cells and reduce treatment efficacy. microRNAs are a subtype of small noncoding RNAs with ∼22 nucleotides that exist among species. They have diverse roles in physiological processes, including cellular proliferation and cell death. Moreover, miRNAs have essential roles in resistance to cancer treatment and can strengthen sensitivity to chemotherapeutic drugs and regimens. In colorectal cancer, the co-treatment of oxaliplatin with anti-miR-19a can partially reverse the oxaliplatin resistance through the upregulation of phosphatase and tensin homolog (PTEN). Moreover, by preventing the spread of gastric cancer cells and downregulating glypican-3 (GPC3), MiR-4510 may modify immunosuppressive signals in the tumor microenvironment. Treatment with oxaliplatin may develop into a specialized therapeutic drug for patients with miR-4510 inhibition and glypican-3-expressing gastric cancer. Eventually, miR-122 upregulation or Wnt/ß-catenin signaling suppression boosted the death of HCC cells and made them more sensitive to oxaliplatin. Herein, we have reviewed the role of microRNAs in regulating cancer cells' response to oxaliplatin, with particular attention to gastrointestinal cancers. We also discussed the role of these noncoding RNAs in the pathophysiology of oxaliplatin-induced neuropathic pain.

miRNAs and Multiple Myeloma: Focus on the Pathogenesis, Prognosis, and Drug Resistance.

Multiple myeloma (MM) produces clonal plasma cells and aberrant monoclonal antibody accumulation in patients' bone marrow (BM). Around 1% of all cancers and 13% of hematological malignancies are caused by MM, making it one of the most common types of cancer. Diagnostic and therapeutic methods for managing MM are currently undergoing extensive research. MicroRNAs (miRNAs) are short noncoding RNAs that reduce or inhibit the translation of their target mRNA after transcription. Because miRNAs play an influential role in how myeloma develops, resources, and becomes resistant to drugs, miRNA signatures may be used to diagnose, do prognosis, and treat the myeloma response. Consequently, researchers have investigated the levels of miRNA in plasma cells from MM patients and developed tools to test whether they directly impacted tumor growth. This review discusses the latest discoveries in miRNA science and their role in the development of MM. We also emphasize the potential applications of miRNAs to diagnose, prognosticate, and treat MM in the future.