Background: Long noncoding RNAs (lncRNAs) contribute to the initiation and progression of gastric cancer (GC). The purpose of this study is to examine the potential role of lncRNA colorectal neoplasia differentially expressed (CRNDE) in modulating the expression of migration and invasion enhancer 1 (MIEN1) through the suppression of miR-136-5p in GC. Methods: The biological roles of CRNDE, miR-136-5p, and MIEN1 in GC were assessed both in laboratory settings and through the examination of clinical samples. Results: CRNDE was found to be significantly increased in GC tissues, and this upregulation was associated with an unfavorable prognosis of GC patients. In vitro experiments showed that inhibiting cell growth and migration, along with promoting apoptosis in GC cells, could be achieved by either disabling CRNDE or MIEN1, or by increasing the expression of miR-136-5p. MIEN1 is a specific recipient of miR-136-5p, and the anticancer effects of miR-136-5p can be counteracted by the increased expression of MIEN1. Through the examination of clinical specimens, it has been observed that there is a significant positive correlation between the expression of MIEN1 and CRNDE. In contrast, miR-136-5p expression in GC tissues shows a negative correlation. Conclusion: A previously unexplored therapeutic target for GC involves the CRNDE/miR-136-5p/MIEN1 signal transduction cascade.

Dysregulation of autophagy has been implicated in the development of many diseases, including cancer. Here, we revealed a novel function of the E3 ubiquitin ligase HRD1 in non-small cell lung carcinoma (NSCLC) metastasis by regulating autophagy. Mechanistically, HRD1 inhibits autophagy by promoting ATG3 ubiquitination and degradation. Additionally, a pro-migratory and invasive factor, MIEN1 (migration and invasion enhancer 1), was found to be autophagically degraded upon HRD1 deficiency. Importantly, expression of both HRD1 and MIEN1 are upregulated and positively correlated in lung tumors. Based on these results, we proposed a novel mechanism of HRD1 function that the degradation of ATG3 protein by HRD1 leads to autophagy inhibition and MIEN1 release, thus promoting NSCLC metastasis. Therefore, our findings provided new insights into the role of HRD1 in NSCLC metastasis and new therapeutic targets for lung cancer treatment.

Drug resistance is a complex phenomenon that frequently develops as a failure to chemotherapy during cancer treatment. Malignant cells increasingly generate resistance to various chemotherapeutic drugs through distinct mechanisms and pathways. Understanding the molecular mechanisms involved in drug resistance remains an important area of research for identification of precise targets and drug discovery to improve therapeutic outcomes. This review highlights the role of some recent emerging targets and pathways which play critical role in driving drug resistance.

The abnormal expression of circular RNAs (circRNAs) is associated with the progression of polycystic ovary syndrome (PCOS), which commonly causes infertility in women. In this study, we identified the role of circ_0030018 in PCOS. Quantitative polymerase chain reaction (qPCR) was used to detect the expression levels of circ_0030018, microRNA (miR)-136, and migration and invasion enhancer 1 (MIEN1). Cell counting kit-8 and 5-ethynyl-2\'-deoxyuridine assays were performed to analyze the proliferation of KGN cells. Apoptosis was analyzed using fluorescence-activated cell sorting. Transwell assays were performed to measure the migration and invasion abilities of cells. qPCR and Western blotting were used to measure the levels of E-cadherin, N-cadherin, Snail, and vimentin. The correlation of circ_0030018 or MIEN1 expression with miR-136 expression was confirmed via luciferase reporter and RNA pull-down assays. Results showed that circ_0030018 expression was upregulated in patients with PCOS and KGN cells. Knockdown of circ_0030018 suppressed the proliferation, migration, and invasion of cells, while promoting their apoptosis. circ_0030018 sponged miR-136, which targeted MIEN1. Moreover, downregulation of miR-136 abrogated the effects of circ_0030018 silencing, while the overexpression of MIEN1 reversed the miR-136-induced effect on KGN cells. In summary, loss of circ_0030018 delayed the progression of PCOS via the miR-136/MIEN1 axis.

To observe the effect of miR-124-5p on progression of gastric cancer (GC) and explore the targeting mechanism.
After collecting the specimens, we used real-time fluorescence quantitative PCR to detect the miR-124-5p level of GC tissue and corresponding adjacent tissue. Then MTT test and scratch wound-healing assay were hired to evaluate the influence of miR-124-5p in GC cell (SGC-803 and SGC7901) migration and proliferation ability. The binding of miR-124-5p to migration and invasion enhancer 1 (MIEN1) was detected through dual luciferase reporter gene experiment and western blot was utilized to assay the protein level of MIEN1.
Compared with adjacent tissues, miR-124-5p level in GC tissues was lower significantly. MiR-124-5p mimic inhibited the metastasis and proliferation ability of SGC7901 cells and miR-124-5p inhibitor promoted the migration and proliferation ability of SGC803 cells. In addition, miR-124-5p targeted MIEN1 and negatively modulated the MIEN1 expression in SGC-803 and SGC7901 cells. Silencing MIEN1 negatively regulated the metastasis and proliferation ability of SGC7901 cells.
MiR-124-5p inhibited the GC cell proliferation and metastasis phenotypes through MIEN1, which probably becomes a novel molecular target for clinical GC treatment.

Previous reports have revealed that circRNA_100876 was extremely important in the progression of triple-negative breast cancer. Nevertheless, the mechanism towards the role of circRNA_100876 in Gastric cancer (GC) remains unknown. Here, we determined circRNA_100876 expression by quantitative real-time PCR (qRT-PCR) in twenty pairs of GC tissues and adjacent tissues. Our data indicated that the expression of circRNA_100876 was raised in GC tissues. In vitro, functional experiments confirmed that cell proliferation, invasion along with migration was promoted by circRNA_100876 in GC tissues. Simultaneously, relative luciferase assay uncovered that circRNA_100876 functioned as a sponge for miR-136, followed by retarding miR-136-induced inhibited effects on the corresponding target, MIEN1. Moreover, we revealed that the expression of MIEN1 was up-regulated and correlated to much worse prognosis of GC. Collectively, our data identified that the promotion of GC growth and metastasis induced by circRNA_100876 interacted with miR-136 and MIEN1, indicating an emerging announcement for uncovering the potential mechanism of GC progression.

: Migration and invasion enhancer 1 (MIEN1) is a membrane-anchored protein and exists in various cancerous tissues. However, the roles of MIEN1 in prostate cancer have not yet been clearly addressed. We determined the expression, biological functions, and regulatory mechanisms of MIEN1 in the prostate. The results of immunohistochemical analysis indicated that MIEN1 was expressed specifically in epithelial cells and significantly higher in adenocarcinoma as compared to in normal tissues. MIEN1 enhanced in vitro cell proliferation, invasion, and in vivo tumorigenesis. Meanwhile, MIEN1 attenuated cisplatin-induced apoptosis in PC-3 cells. Overexpression of NF-ĸB-inducing kinase (NIK) enhanced MIEN1 expression, while overexpression of NF-ĸB inhibitor α (IĸBα) blocked MIEN1 expression in PC-3 cells. In prostate carcinoma cells, MIEN1 provoked Akt phosphorylation; moreover, MIEN1 downregulated N-myc downstream regulated 1 (NDRG1) but upregulated interleukin-6 (IL-6) gene expression. MK2206, an Akt inhibitor, impeded the modulation of MIEN1 on NDRG1 and IL-6 expressions. Our studies suggest that MIEN1 is an NF-ĸB downstream oncogene in the human prostate. Accordingly, the modulation of Akt signaling in the gene expressions of NDRG1 and IL-6 may account for the functions of MIEN1 in cell proliferation, invasion, and tumorigenesis in prostate carcinoma cells.

Tumor metastasis is a sequential event accounting for numerous cancer-related fatalities worldwide. The process of metastasis serially involves invasion, intravasation, extravasation, and tumor growth at the secondary site. Migration and invasion enhancer 1 (MIEN1) is a membrane associated protein overexpressed in various human cancers. Biological activity of MIEN1 is driven by geranylgeranyltransferase-I mediated prenylation at CAAX motif and methylation of the prenylated protein that anchors MIEN1 into the cellular membrane. Post-translationally modified MIEN1 interacts with Syk kinase and Annexin A2 protein; polymerizes G-actin and stabilizes F-actin filament; induces focal adhesion kinase phosphorylation and decrease cofilin phosphorylation implicated in both invasion and metastasis of different cancer types. In the present review, we discuss the structure, function, and involvement of MIEN1 in cancer progression. We also highlight the future prospects of MIEN1 as an emerging molecule and novel target in cancer cell invasion and metastasis.

MIEN1 is a novel oncogene, and it involves tumor progression in various cancer types, including colon cancer. However, the definite molecular mechanisms of MIEN1 in colon cancer progression remain to be completely elucidated. In the present study, bioinformatics prediction showed that miR-136 could be an upstream regulator of MIEN1; a luciferase assay and Western blot assay revealed that miR-136 negatively regulates MIEN1 expression via directly targeting its 3\'-untranslated region sequence. Moreover, a functional assay using wound healing and transwell invasion showed that overexpressed miR-136 inhibited cell migration and invasion, and overexpression of MIEN1 partly rescued the above-mentioned effects of miR-136 in colon cancer cells. Additionally, a clinical sample assay showed that miR-136 expression was generally downregulated in colon cancer tissue, which was inversely correlated with MIEN1 expression. Furthermore, we found that miR-136 suppressed the Akt/NF-κB signaling pathway and epithelial-to-mesenchymal transition in colon cancer. These results suggest that miR-136, as a tumor suppressor, acts in tumor metastasis by suppressing MIEN1 expression in colon cancer, providing a novel target for the treatment of colon cancer.

Migration and invasion enhancer 1 (MIEN1) is a novel gene involved in prostate cancer progression by enhancing prostate cancer cell migration and invasion. DNA methylation, an important epigenetic regulation, is one of the most widely altered mechanisms in prostate cancer. This phenomenon frames the basis to study the DNA methylation patterns in the promoter region of MIEN1. Bisulfite pyrosequencing demonstrates the MIEN1 promoter contains a short interspersed nuclear Alu element (SINE Alu) repeat sequence. Validation of methylation inhibition on MIEN1 was performed using nucleoside analogs and non-nucleoside inhibitors and resulted in an increase in both MIEN1 RNA and protein in normal cells. MIEN1 mRNA and protein increases upon inhibition of individual DNA methyltransferases using RNA interference technologies. Furthermore, dual luciferase reporter assays, in silico analysis, and chromatin immunoprecipitation assays identified a sequence upstream of the transcription start site that has a site for binding of the USF transcription factors. These results suggest the MIEN1 promoter has a SINE Alu region that is hypermethylated in normal cells leading to repression of the gene. In cancer, the hypomethylation of a part of this repeat, in addition to the binding of USF, results in MIEN1 expression.