Colorectal cancer (CRC) is a common malignancy with 1. 8 million cases in 2018. Autophagy helps to maintain an adequate cancer microenvironment in order to provide nutritional supplement under adverse conditions such as starvation and hypoxia. Additionally, most of the cases of CRC are unresponsive to chemotherapy, representing a significant challenge for cancer therapy. Recently, autophagy induced by therapy has been shown as a unique mechanism of resistance to anticancer drugs. In this regard, long non-coding RNAs (lncRNAs) analysis are important for cancer detection, progression, diagnosis, therapy response, and prognostic values. With increasing development of quantitative detection techniques, lncRNAs derived from patients' non-invasive samples (i.e., blood, stools, and urine) has become into a novel approach in precision oncology. Tumorspecific GAS5, HOTAIR, H19, and MALAT are novels CRC related lncRNAs detected in patients. Nonetheless, the effect and mechanism of lncRNAs in cancer autophagy and chemoresistance have not been extensively characterized. Chemoresistance and autophagy are relevant for cancer treatment and lncRNAs play a pivotal role in resistance acquisition for several drugs. LncRNAs such as HAGLROS, KCNQ1OT1, and H19 are examples of lncRNAs related to chemoresistance leaded by autophagy. Finally, clinical implications of lncRNAs in CRC are relevant, since they have been associated with tumor differentiation, tumor size, histological grade, histological types, Dukes staging, degree of differentiation, lymph node metastasis, distant metastasis, recurrent free survival, and overall survival (OS).

Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.

Cancer stem cells (CSCs) are able to promote initiation, survival and maintenance of tumor growth and have been involved in gastrointestinal cancers (GICs) such as esophageal, gastric and colorectal. It is well known that blood supply facilitates cancer progression, recurrence, and metastasis. In this regard, tumor-induced angiogenesis begins with expression of pro-angiogenic molecules such as vascular endothelial growth factor (VEGF), which in turn lead to neovascularization and thus to tumor growth. Another pattern of blood supply is called vasculogenic mimicry (VM). It is a reminiscent of the embryonic vascular network and is carried out by CSCs that have the capability of transdifferentiate and form vascular-tube structures in absence of endothelial cells. In this review, we discuss the role of CSCs in angiogenesis and VM, since these mechanisms represent a source of tumor nutrition, oxygenation, metabolic interchange and facilitate metastasis. Identification of CSCs mechanisms involved in angiogenesis and VM could help to address therapeutics for GICs.

Chemotherapy activates a novel cytoplasmic DNA damage response resulting in Golgi apparatus fragmentation and cancer cell survival. This mechanism is regulated by Golgi phosphoprotein-3 (GOLPH3)/Myo18A/F-actin axis. Analyzing the functions of miR-3135b, a small non-coding RNA with unknown functions, we found that its forced overexpression attenuates the Golgi apparatus fragmentation induced by chemotherapeutic drugs in colorectal cancer (CRC) cells. First, we found that miR-3135b is downregulated in CRC cell lines and clinical tumors. Bioinformatic predictions showed that miR-3135b could be regulating protein-encoding genes involved in cell survival, resistance to chemotherapy, and Golgi dynamics. In agreement, ectopic transfection of miR-3135b in HCT-15 cancer cells significantly inhibited cell proliferation, sensitized cells to 5-fluoruracil (5-FU), and promoted late apoptosis and necrosis. Also, miR-3135b overexpression impaired the cell cycle progression in HCT-15 and SW-480 cancer cells. Because GOLPH3, a gene involved in maintenance of Golgi structure, was predicted as a potential target of miR-3135b, we studied their functional relationships in response to DNA damage induced by chemotherapy. Immunofluorescence and cellular ultrastructure experiments using antibodies against TGN38 protein, a trans-Golgi network marker, showed that 5-FU and doxorubicin treatments result in an apoptosis-independent stacks dispersal of the Golgi ribbon structure in both HCT-15 and SW-480 cells. Remarkably, these cellular effects were dramatically hindered by transfection of miR-3135b mimics. In addition, our functional studies confirmed that miR-3135b binds to the 3′-UTR of GOLPH3 proto-oncogene, and also reduces the levels of p-AKT1 (Ser473) and p-mTOR (Ser2448) signaling transducers, which are key in cell survival and autophagy activation. Moreover, we found that after treatment with 5-FU, TGN38 factor coimmunolocalizes with beclin-1 autophagic protein in discrete structures associated with the fragmented Golgi, suggesting that the activation of pro-survival autophagy is linked to loss of Golgi integrity. These cellular effects in autophagy and Golgi dispersal were reversed by miR-3135b. In summary, we provided experimental evidence suggesting for the first time a novel role for miR-3135b in the protection of chemotherapy-induced Golgi fragmentation via GOLPH3/AKT1/mTOR axis and protective autophagy in colorectal cancer cells.

Interleukin-10 (IL-10) gene polymorphisms have been associated with severity and outcomes in patients with respiratory and nonrespiratory viral infections. The aim of this study was to assess whether rs1800871 and rs1800872 polymorphisms of IL-10 gene are associated with the clinical outcomes of COVID-19 in a Mexican population. Study subjects were 193 COVID-19 patients. The genotyping was carried out with real-time PCR and serum IL-10 levels were measured with enzyme-linked immunosorbent assay. Logistic regression analysis was used for analysis association with clinical outcomes. There was no evidence of an association between alleles, genotypes, or haplotypes frequencies between patient groups according to severity and outcomes. The rs1800871 and rs1800872 polymorphisms might not be genetic risk factors for severity and mortality for COVID-19 in Mexican mestizos patients from northwest Mexico.