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Abstract MicroRNA-98 (miR-98) stands as an important molecule in the intricate landscape of oncology. As a subset of microRNAs, these small non-coding RNAs have accompanied a new era in cancer research, underpinning their significant roles in tumorigenesis, metastasis, and therapeutic interventions. This review provides a comprehensive insight into the biogenesis, molecular properties, and physiological undertakings of miR-98, highlighting its double-edged role in cancer progression—acting both as a tumor promoter and suppressor. Intriguingly, miR-98 has profound implications for various aspects of cancer progression, modulating key cellular functions, including proliferation, apoptosis, and the cell cycle. Given its expression patterns, the potential of miR-98 as a diagnostic and prognostic biomarker, especially in liquid biopsies and tumor tissues, is explored, emphasizing the hurdles in translating these findings clinically. The review concludes by evaluating therapeutic avenues to modulate miR-98 expression, addressing the challenges in therapy resistance, and assessing the efficacy of miR-98 interventions. In conclusion, while miR-98’s involvement in cancer showcases promising diagnostic and therapeutic avenues, future research should pivot towards understanding its role in tumor-stroma interactions, immune modulation, and metabolic regulation, thereby unlocking novel strategies for cancer management. Graphical Abstract

MicroRNA-98 (miR-98) stands as an important molecule in the intricate landscape of oncology. As a subset of microRNAs, these small non-coding RNAs have accompanied a new era in cancer research, underpinning their significant roles in tumorigenesis, metastasis, and therapeutic interventions. This review provides a comprehensive insight into the biogenesis, molecular properties, and physiological undertakings of miR-98, highlighting its double-edged role in cancer progression—acting both as a tumor promoter and suppressor. Intriguingly, miR-98 has profound implications for various aspects of cancer progression, modulating key cellular functions, including proliferation, apoptosis, and the cell cycle. Given its expression patterns, the potential of miR-98 as a diagnostic and prognostic biomarker, especially in liquid biopsies and tumor tissues, is explored, emphasizing the hurdles in translating these findings clinically. The review concludes by evaluating therapeutic avenues to modulate miR-98 expression, addressing the challenges in therapy resistance, and assessing the efficacy of miR-98 interventions. In conclusion, while miR-98's involvement in cancer showcases promising diagnostic and therapeutic avenues, future research should pivot towards understanding its role in tumor-stroma interactions, immune modulation, and metabolic regulation, thereby unlocking novel strategies for cancer management. [ABSTRACT FROM AUTHOR]

AbstractObjective Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells.Methods An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays.Results NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation.Conclusion The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.

Cell maintenance and the establishment of cell polarity involve complicated interactions among multiple protein complexes as well as the regulation of different signaling pathways. As an important cell polarity protein, Par3 is evolutionarily conserved and involved in tight junction formation as well as tumorigenesis. In this review, we aimed to explore the function of Par3 in tumorigenesis. Research has shown that Par3 exhibits dual functions in human cancers, both tumor-promoting and tumor-suppressive. Here, we focus on the activities of Par3 in different stages and types of tumors, aiming to offer a new perspective on the molecular mechanisms that regulate the functions of Par3 in tumor development. Tumor origin, tumor microenvironment, tumor type, cell density, cell–cell contact, and the synergistic effect of Par3 and other tumor-associated signaling pathways may be important reasons for the dual function of Par3. The important role of Par3 in mammalian tumorigenesis and potential signaling pathways is context dependent. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) begins within the organ of the pancreas, which produces digestive enzymes, and is one of the formidable cancers for which appropriate treatment strategies are urgently needed. Autophagy occurs in the many chambers of PC tissue, including cancer cells, cancer-related fibroblasts, and immune cells, and can be fine-tuned by various promotive and suppressive signals. Consequently, the impacts of autophagy on pancreatic carcinogenesis and progression depend greatly on its stage and conditions. Autophagy inhibits the progress of preneoplastic damage during the initial phase. However, autophagy encourages tumor formation during the development phase. Several studies have reported that both a tumor-promoting and a tumor-suppressing function of autophagy in cancer that is likely cell-type dependent. However, autophagy is dispensable for pancreatic ductal adenocarcinoma (PDAC) growth, and clinical trials with autophagy inhibitors, either alone or in combination with other therapies, have had limited success. Autophagy's dual mode of action makes it therapeutically challenging despite autophagy inhibitors providing increased longevity in medical studies, highlighting the need for a more rigorous review of current findings and more precise targeting strategies. Indeed, the role of autophagy in PC is complicated, and numerous factors must be considered when transitioning from bench to bedside. In this review, we summarize the evidence for the tumorigenic and protective role of autophagy in PC tumorigenesis and describe recent advances in the understanding of how autophagy may be regulated and controlled in PDAC. [ABSTRACT FROM AUTHOR]

Abstract MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.

microRNAs are endogenous, noncoding RNAs. Showing both tumor‐suppressive and oncogenic characteristics, miRNAs can regulate important processes in malignancies. This review aimed at highlighting the recent studies on the contribution of miR‐424 to the modulation of carcinogenesis and exploring its probable clinical effectiveness in the diagnosis and therapy of malignancies. The data were extracted from all papers published from 2013 until 2020. Mature miR‐424 leads to the degradation of its target transcripts or the suppression of translation via binding to the molecular targets. miR‐424 is involved in modulating p53, PI3K/Akt, Wnt, and other molecular pathways, thereby regulating cellular growth, apoptosis, differentiation, chemoresistance, and cancer immunity. miR‐424 was introduced as a tumor‐suppressive miR in numerous types of cancers while as an oncogene in several cancers. Regarding the cancer dependent role of miR‐424, it may be a prognostic and diagnostic biomarker and a potential candidate for the treatment of cancers. [ABSTRACT FROM AUTHOR]

The paper in hand seeks to evaluate the tumor-suppressive and apoptotic effects of L. paracasei X12 in 1, 2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. The rats were divided into three groups (n = 8-12 per group); L. paracasei X12 was administrated to these animals for forty weeks. The findings of this study indicated that L. paracasei X12 administration prevented severe weight loss in DMH-treated rats. It was also determined that L. paracasei X12 administration could prevent the neoplasia incidence, cell proliferation and it also could suppress the tumors' growth. Additionally, a significant improvement was observed in apoptosis indexes and cell proliferation in probiotic-treated rats. In conclusion, this study provides insights into the therapeutic potential of L. paracasei X12 with emphasis on the issue that modulation of apoptosis pathway could leave beneficial effects in the prevention and suppression of colorectal cancer (CRC). However, further studies are in support to clarify the mechanisms involved in the tumor-suppressive effect of probiotics. [ABSTRACT FROM AUTHOR]

MicroRNAs are a set of highly conserved non-coding RNAs that control gene expression at the post-transcriptional/translational levels by binding to the 3′-UTR of diverse target genes. Increasing evidence indicates that miRNAs not only play a vital role in many biological processes, but they are also frequently deregulated in pathological conditions, including cancer. The miR-320 family is one of many tumor suppressor families and is composed of five members, which has been demonstrated to be related to the repression of epithelial-mesenchymal transition (EMT) inhibition, cell proliferation, and apoptosis. Moreover, this family has been shown to regulate drug resistance, and act as a potential biomarker for the diagnosis, prognosis, and prediction of cancer. In this review, we summarized recent research with reference to the tumor suppressor function of miR-320 and the regulation mechanisms of miR-320 expression. The collected evidence shown here supports that miR-320 may act as a novel biomarker for cancer prognosis and therapeutic response to cancer treatment.

Endometrial cancer (EC), a prevalent gynecologic tumor, is a great threat to women. We aimed to explore miR-142's effects on EC and the relevant mechanisms. Cell proliferation was evaluated with MTT, cell counting, and colony formation assay. MRNA abundances of miR-142 and cyclin D1 (CCND1) were examined with quantitative real-time PCR. CCND1 protein level in cells was analyzed with Western blot. miR-142's downstream target was identified with targetscan and luciferase reporter assay. Nude mice were injected subcutaneously with Ishikawa (ISK) cells transfected with or without miR-142 mimics. Ki-67 and CCND1 expressions in tumors of xenograft mice were analyzed with immunohistochemical assay. miR-142 was expressed at a lower level in human EC tumor samples than matched normal tissues, and its mRNA level in EC patients without metastasis was higher than that in patients with metastatic EC. Additionally, low-level miR-142 was closely linked with the poor prognosis of EC patients. miR-142 restricted ISK and HEC-1A cell proliferation. Targetscan and luciferase reporter assay proved the target relationship between miR-142 and CCND1. Moreover, high-level CCND1 was positively correlated with the poor prognosis of EC patients. Besides, miR-142 mimics restricted tumor growth in ISK xenografted mice, as well as inhibited the expression of Ki67 and CCND1 in excised tumors. miR-142 restricted EC proliferation by targeting CCND1. [ABSTRACT FROM AUTHOR]

Autophagy is an evolutionarily conserved, multi-step lysosomal degradation process for the clearance of damaged or superfluous proteins and organelles. Accumulating studies have recently revealed that autophagy is closely related to a variety of types of cancer; however, elucidation of its Janus role of either tumor-suppressive or tumor-promoting still remains to be discovered. In this review, we focus on summarizing the context-dependent role of autophagy and its complicated molecular mechanisms in different types of cancer. Moreover, we discuss a series of small-molecule compounds targeting autophagy-related proteins or the autophagic process for potential cancer therapy. Taken together, these findings would shed new light on exploiting the intricate mechanisms of autophagy and relevant small-molecule compounds as potential anti-cancer drugs to improve targeted cancer therapy. [ABSTRACT FROM AUTHOR]

1,25-Dihydroxyvitamin D3 has been known to have the tumor-suppressive activity in various kinds of tumors. However, the exact effect and working mechanism of 1,25-dihydroxyvitamin D3 on the tumor-suppressive activity in human kidney cancer cells remains poorly understood. 1,25-Dihydroxyvitamin D3 has cytotoxicity to ACHN cells and inhibited ACHN cell proliferation compared to the vehicle control. 1,25-Dihydroxyvitamin D3 increased the expression of the cleaved PARP1, active Caspase3, Bax, and Bim but decreased the expression of Bcl2 in ACHN cells. Moreover, 1,25-dihydroxyvitamin D3 down-regulated the phosphorylated Akt and Erk which might lead to apoptosis through activation of FOXO3 in ACHN cells. Transfection of siRNA against FOXO3 attenuated the pro-apoptotic BimEL expression in ACHN cells treated with 1,25-dihydroxyvitamin D3. These results suggest that FOXO3 is involved in the apoptosis induced by 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 causes apoptosis in kidney cancer cells with a FOXO3-dependent manner. [ABSTRACT FROM PUBLISHER]

MicroRNAs are a set of highly conserved non-coding RNAs that control gene expression at the post-transcriptional/translational levels by binding to the 3′-UTR of diverse target genes. Increasing evidence indicates that miRNAs not only play a vital role in many biological processes, but they are also frequently deregulated in pathological conditions, including cancer. The miR-320 family is one of many tumor suppressor families and is composed of five members, which has been demonstrated to be related to the repression of epithelial-mesenchymal transition (EMT) inhibition, cell proliferation, and apoptosis. Moreover, this family has been shown to regulate drug resistance, and act as a potential biomarker for the diagnosis, prognosis, and prediction of cancer. In this review, we summarized recent research with reference to the tumor suppressor function of miR-320 and the regulation mechanisms of miR-320 expression. The collected evidence shown here supports that miR-320 may act as a novel biomarker for cancer prognosis and therapeutic response to cancer treatment. [ABSTRACT FROM AUTHOR]

MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected. [ABSTRACT FROM AUTHOR]