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The Hippo signaling pathway has a regulatory function in the organogenesis process and cellular homeostasis, switching the cascade reactions of crucial kinases acts to turn off/on the Hippo pathway, altering the downstream gene expression and thereby regulating proliferation, apoptosis, or stemness. Disruption of this pathway can lead to the occurrence of various disorders and different types of cancer. Recent findings highlight the importance of ncRNAs, such as microRNA, circular RNA, and lncRNAs, in modulating the Hippo pathway. Defects in ncRNAs can disrupt Hippo pathway balance, increasing tumor cells, tumorigenesis, and chemotherapeutic resistance. This review summarizes ncRNAs' inhibitory or stimulatory role in - Hippo pathway regulation in cancer and stem cells. Identifying the relation between ncRNAs and the components of this pathway could pave the way for developing new biomarkers in the treatment and diagnosis of cancers.

Abstract In recent decades, colorectal cancer (CRC) has turned into one of the most widespread malignancies, and the incidence of this malignancy is expected to increase. Despite considerable improvements in therapeutic approaches, the prognosis, and the management of CRC face many problems. Likely, the main limitation in the successful treatment of CRC is the lack of appropriate clinical therapeutic targets. As an effective target, the signal transducer and activator of transcription 3 (STAT3) are regulated by a wide range of genes and involved in cellular processes, including cell growth, migration, invasion, immunosuppression, and angiogenesis. Aberrant regulation of STAT3 signaling leads to cellular dysfunction, diseases, and malignancies, including CRC. Consequently, targeting this signaling pathway is considered one of the therapeutic strategies used in CRC treatment. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are non-coding RNA molecules with partial or no protein-coding activity that participate in gene regulation at epigenetic, transcriptional, and post-transcriptional levels and regulate multiple signaling pathways, including STAT3 signaling (especially JAK/STAT). Therefore, these regulatory molecules are suggested to be very promising targets to present new insights into overcoming the limitations of conventional therapeutic strategies. Therefore, the current review study aimed to summarize the therapeutic and diagnostic significance of miRNAs and lncRNAs and their therapeutic and diagnostic significance related to the expression and activity of STAT3 in CRC.

Abstract A wide range of studies have indicated that microRNAs (miRNAs), a type of small single-stranded regulatory RNAs, are dysregulated in a different variety of human cancers. Therefore, they are expected to play important roles in tumorigenesis by functioning as oncogenic (oncomiRs) or tumor-suppressive miRNAs. Subsequently, their potential as diagnostic and therapeutic targets for malignancies has attracted attention in recent years. In particular, studies have revealed the aberrant expression of miR-182 through tumorigenesis and its important roles in various aspects of malignancies, including proliferation, metastasis, and chemoresistance. Accumulating reports have illustrated that miR-182, as a dual-role regulator, directly or indirectly regulates the expression of a wide range of genes and modulates the activity of various signaling pathways involved in tumor progression, such as JAK / STAT3, Wnt / β-catenin, TGF-β, and P13K / AKT. Therefore, considering the high therapeutic and diagnostic potential of miR-182, this review aims to point out the effects of miR-182 dysregulation on the signaling pathways involved in tumorigenesis.

Purpose: CD44 plays a pivotal role through tumorigenesis by regulating cancer cell metastasis, stemness, and chemosensitivity and is considered a promising therapeutic target for human cancers, including colorectal cancer (CRC). Therefore, the present research aimed to examine the simultaneous therapeutic effect of CD44 silencing and 5-fluorouracil (5-FU) on in vitro tumorigenesis of CRC cells. Methods: CD44 expression was initially evaluated in TCGA datasets and CRC tissues. Furthermore, functional analysis was performed on HT-29 CRC cells overexpressing CD44. The cells were transfected with CD44 siRNA and then treated with 5-FU. Consequently, to explore the combination therapy effect on cell viability, migration, apoptosis, and chromatin fragmentation, we performed MTT assay, scratch assay, Annexin V/PI staining and DAPI staining assays, respectively. The spheroid and colony formation assays were further employed to investigate stemness features. The gene expression at protein and mRNA levels were explored using western blotting and qPCR. Results: Our findings illustrated that CD44 was significantly overexpressed in CRC tissues compared to normal samples. The suppression of CD44 considerably promoted the chemosensitivity of HT-29 cells to 5-FU by apoptosis induction. Also, the combination therapy led to overexpression of apoptotic genes, including P53, caspase-3, and caspase-9, as well as downregulation of AKT1 expression. Furthermore, CD44 suppression, separately or combined with 5-FU, hindered stemness properties in HT-29 cells via downregulation of Sox2 and Nanog expression. Besides, the combination therapy remarkably downregulated MMPs and suppressed CRC cell migration. Conclusion: Considering its involvement in chemosensitivity to 5-FU, CD44 could be suggested as a potential target for improving the efficiency of CRC chemotherapy.

Introduction: As the most common aggressive primary brain tumor, glioblastoma is inevitably a recurrent malignancy whose patients’ prognosis is poor. miR-143 and miR-145, as tumor suppressor miRNAs, are downregulated through tumorigenesis of multiple human cancers, including glioblastoma. These two miRNAs regulate numerous cellular processes, such as proliferation and migration. This research was intended to explore the simultaneous replacement effect of miR-143, and miR-145 on in vitro tumorgenicity of U87 glioblastoma cells. Methods: U87 cells were cultured, and transfected with miR-143-5p and miR-145-5p. Afterward, the changes in cell viability, and apoptosis induction were determined by MTT assay and Annexin V/PI staining. The accumulation of cells at the cell cycle phases was assessed using the flow cytometry. Wound healing and colony formation assays were performed to study cell migration. qRT-PCR and western blot techniques were utilized to quantify gene expression levels. Results: Our results showed that miR-143-5p and 145-5p exogenous upregulation cooperatively diminished cell viability, and enhanced U-87 cell apoptosis by modulating Caspase-3/8/9, Bax, and Bcl-2 protein expression. The combination therapy increased accumulation of cells at the sub-G1 phase by modulating CDK1, Cyclin D1, and P53 protein expression. miR-143/145-5p significantly decreased cell migration, and reduced colony formation ability by the downregulation of c-Myc and CD44 gene expression. Furthermore, the results showed the combination therapy of these miRNAs could remarkably downregulate phosphorylated-AKT expression levels. Conclusion: In conclusion, miR-143 and miR-145 were indicated to show cooperative anti- cancer effects on glioblastoma cells via modulating AKT signaling as a new therapeutic approach.

As a disease with the highest disease-associated burden worldwide, cancer has been the main subject of a considerable proportion of medical research in recent years, intending to find more effective therapeutic approaches with fewer side effects. Combining conventional methods with newer biologically based treatments such as immunotherapy can be a promising approach to treating different tumors. The concept of “cancer immunoediting” that occurs in the field of the tumor microenvironment (TME) is the aspect of cancer therapy that has not been at the center of attention. One group of the role players of the so-called immunoediting process are the immune checkpoint molecules that exert either co-stimulatory or co-inhibitory effects in the anti-tumor immunity of the host. It involves alterations in a wide variety of immunologic pathways. Recent studies have proven that conventional cancer therapies, such as chemotherapy, radiotherapy, or a combination of them, i.e., chemoradiotherapy, alter the “immune compartment” of the TME. The mentioned changes encompass a wide range of variations, including the changes in the density and immunologic type of the tumor-infiltrating lymphocytes (TILs) and the alterations in the expression patterns of the different immune checkpoints. These rearrangements can have either anti-tumor immunity empowering or immune attenuating sequels. Thus, recognizing the consequences of various chemo(radio)therapeutic regimens in the TME seems to be of great significance in the evolution of therapeutic approaches. Therefore, the present review intends to summarize how chemo(radio)therapy affects the TME and specifically some of the most important, well-known immune checkpoints’ expressions according to the recent studies in this field.

Purpose: Based on WHO report, colorectal cancer (CRC) is the second cause of death among patients with cancer worldwide. Dysregulation of miRNAs expressions has been demonstrated in different human cancers, especially CRC. Studies have shown that miR-330 could act as both TS-miR and/or oncomiR in different types of cancers. BACH1 is also identified as a transcription factor, which is involved in ontogenesis. In this study, we evaluated the CRC suppression via silencing of BACH1 by small silencer molecule called miR-330. Methods: Firstly, we analyzed the BACH1, miR-330-3p and miR-330-5p expressions according to the colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) project established from a patient of the colon and rectal cancer patients in The Cancer Genome Atlas (TCGA) database. The targeting of BACH1 via miR-330 in human CRC cells was evaluated by Vejnar bioinformatics methods, and confirmed by qRT-PCR and western blot analysis. Proliferation was performed by MTT assay. The MMP9, CXCR4, and VEGFR proteins were measured by western blotting. Results: The analysis of BACH1, miR-330-3p, and miR-330-5p expressions according to the COAD and READ projects showed that BACH1 was overexpressed, but miR-330-3p and miR330-5p were reduced in CRC tumors compared to normal controls. The miR-330 induction prevented proliferation of CRC cell by targeting BACH1 mRNA, which represses MMP9, C-X-C chemokine receptor type 4 (CXCR4), and vascular endothelial growth factor receptor (VEGFR) proteins expressions. Conclusion: Our results suggested that BACH1 is a potential target for miR-330 in CRC cells. The miR-330 induction inhibits CRC cells proliferation by suppressing BACH1 expression in posttranscriptional level. It was suggested that targeting of BACH1 via miRNA such as miR-330 could be a valid strategy in the field of CRC targeted therapy via modulating the oncogenic signaling pathway.

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) in China, which spread to the rest of the world, led the World Health Organization to classify it as a global pandemic. COVID-19 belongs to the Bettacoronavirus genus of the Coronaviridae family, and it mainly spreads through the respiratory tract. Studies have now confirmed a human-to-human transmission as the primary pathway of spread. COVID-19 patients with a history of diseases such as respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit requiring invasive ventilation or even death). The current focus has been on the development of novel therapeutics, including antivirals, monoclonal antibodies, and vaccines. However, although there is undoubtedly an urgent need to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases from which these patients may suffer, including cancer. This review summarizes the current evidence regarding the epidemiology, pathogenesis, and management of patients with COVID-19. It also aims to provide the reader with insights into COVID-19 in pregnant patients and those with cancer, outlining necessary precautions relevant to cancer patients. Finally, we provide the available evidence on the latest potent antiviral drugs and vaccines of COVID-19 and the ongoing drug trials.