L��� ���-������ RNA� ����RNA�� ��� ����� ����-L��� ���-������ RNA� ����RNA�� ��� ����� ����tified potential biological and gene regulators. Similar to other cell-free circulating cancer-related nucleic acids, lncRNAs are released in the peripheral circulation of cancer patients and allow for non-invasive gene expression assessment. lncRNAs are considered to be promising biomarkers for cancer prognosis and diagnosis. Several lncRNAs have been found to regulate developmental processes in a number of biological disorders. Recent studies indicated that lncRNAs are associated with numerous diseases, most notably cancer, as they were found to be highly expressed or silenced in a number of human cancers, including colorectal cancer (CRC). Despite advances in the current detection methods, over half of cancer patients succumb to the disease, as several CRC cases are diagnosed at an advanced stage. Due to the lack of non-invasive and low-cost prognostic and diagnostic tests for CRC, the identification of novel, potentially effective biomarkers has been attracting increasing attention in recent cancer research. The present review focused on the most widely applied lncRNAs in cancer detection, including CRC, in vitro.

The regulation of Lp(a) clearance from circulation by cellular uptake remains enigmatic. While multiple receptors have been implicated in Lp(a) uptake, each receptor only partially accounts for this uptake, and no endocytic mechanism has yet been prescribed for Lp(a) internalisation into the cell. In this study, we define macropinocytosis as the endocytic pathway responsible for internalising Lp(a). In both liver and macrophage cells, Lp(a) uptake is dependent on extracellular calcium and is inhibited by amiloride or its derivative EIPA. The uptake of apo(a) alone is mediated by macropinocytosis, indicating the apo(a) protein component is a primary regulator of Lp(a) uptake. Importantly, we found that common antidepressants modulate Lp(a) macropinocytosis in cell-type dependent manners. In macrophages, the tricyclic antidepressant, imipramine and selective serotonin reuptake inhibitors (SSRIs) citalopram, fluoxetine and sertraline all inhibit Lp(a) uptake. In liver cells, imipramine and citalopram strongly stimulated Lp(a) uptake, while sertraline inhibited uptake. Imipramine and citalopram enhanced Lp(a) uptake by enhancing cell surface binding of Lp(a) rather than upregulating macropinocytosis per se, indicating that immobilisation of Lp(a) on the plasma membrane is an important regulatory step in Lp(a) macropinocytosis. As the liver is the major catabolic route for Lp(a), we dissected the functional consequences of imipramine and citalopram stimulated uptake in liver cells. Both drugs increased Lp(a) delivery to Rab11-positive recycling endosomes, but not late endosomes or lysosomes, resulting in increased apo(a) recycling into the cellular media. Given that free apo(a) is reported to undergo consistent proteolysis in the extracellular space or in circulation, these results support the potential for the already approved drugs, imipramine and citalopram, as promising therapeutics to lower Lp(a) levels. This approach displays special utility in the large group of people who suffer from depression and anxiety for whom these drugs are commonly prescribed.

Endocytosis is the process by which molecules are actively transported into cells. It can take on a variety of forms depending on the cellular machinery involved ranging from specific receptor-mediated endocytosis to the less selective and actin-driven macropinocytosis. The plasma lipoproteins, which deliver lipids and other cargo to cells, have been intensely studied with respect to their endocytic uptake. One of the first molecules to be visualised undergoing endocytosis via a receptor-mediated, clathrin-dependent pathway was low-density lipoprotein (LDL). The LDL molecule has subsequently been shown to be internalised through multiple endocytic pathways. Dissecting the pathways of lipoprotein endocytosis has been crucial to understanding the regulation of plasma lipid levels and how lipids enter cells in the arterial wall to promote atherosclerosis. It has also aided understanding of the dysregulation that occurs in plasma lipid levels when molecules involved in uptake are defective, as is the case in familial hypercholesterolemia (FH). The aim of this review is to outline the many endocytic pathways utilised for lipoprotein uptake. It explores the various experimental approaches that have been applied to visualise lipoprotein endocytosis with an emphasis on LDL and its more complex counterpart, lipoprotein(a) [Lp(a)]. Finally, we look at new developments in lipoprotein visualisation that hold promise for scrutinising endocytic pathways to finer detail in the future.

Among all cancer types, colorectal cancer is the third most common in men and the second most common in women globally. Generally, the risk of colorectal cancer increases with age, and colorectal cancer is modulated by various genetic alterations. Alterations in the immune response serve a significant role in the development of colorectal cancer. In primary cancer types, immune cells express a variety of inhibitory molecules that dampen the immune response against tumor cells. Additionally, few reports have demonstrated that classical chemotherapy promotes the immunosuppressive microenvironment in both tissues and immune cells. This study assessed the expression levels of genes using RT-qPCR associated with the immune system, including interferon-γ, programmed death-1, β2-microglobulin, human leukocyte antigen-A, CD3e, CD28 and intracellular adhesion molecule 1, in patients with colorectal cancer, as these genes are known to serve important roles in immune regulation during cancer incidence. Gene expression analysis was performed with the whole blood cells of patients with colorectal cancer and healthy volunteers. Compared with the normal controls, programmed death-1was highly expressed in patients with advanced-stage colorectal cancer. Furthermore, the expression of programmed death-1 was higher in patients receiving adjuvant therapy, which suggests the therapy dampened the immune response against tumor cells. The results of the present study indicate that classical adjuvant therapies, which are currently used for patients with colorectal cancer, should be modulated, and a combination of classical therapy with anti-programmed death-1 antibody should be conducted for improved management of patients with colorectal cancer.