Striatins (STRNs) are generally considered to be cytoplasmic proteins, with lower expression observed in the nucleus and at cell-cell contact regions. Together with protein phosphatase 2A (PP2A), STRNs form the core region of striatin-interacting phosphatase and kinase (STRIPAK) complexes through the coiled-coil region of STRN proteins, which is crucial for substrate recruitment. Over the past two decades, there has been an increasing amount of research into the biological and cellular functions of STRIPAK members. STRNs and the constituent members of the STRIPAK complex have been found to regulate several cellular functions, such as cell cycle control, cell growth, and motility. Dysregulation of these cellular events is associated with cancer development. Importantly, their roles in cancer cells and clinical cancers are becoming recognised, with several STRIPAK components found to have elevated expression in cancerous tissues compared to healthy tissues. These molecules exhibit significant diagnostic and prognostic value across different cancer types and in metastatic progression. The present review comprehensively summarises and discusses the current knowledge of STRNs and core STRIPAK members, in cancer malignancy, from both cellular and clinical perspectives.

Long non-coding RNAs (lncRNAs) have been shown to participate in the development and progression of several different types of cancer. Past studies indicated that lncRNA MAFG-antisense 1 (AS1) promotes colorectal cancer. However, the role of MAFG-AS1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study is to examine the effect of lncRNA MAFG-AS1 on drug resistance HCC. The results indicated that MAFG-AS1 is upregulated in drug-resistant cells. Further, MAFG-AS1 promotes growth and migration of HCC by upregulating STRN4 through absorbing miR-3196. Thus, LncRNA MAFA-AS1 may become a novel target to treat HCC patients.

Mitogen-activated protein kinase kinase kinase kinases (MAP4Ks) constitute a mammalian STE20-like serine/threonine kinase subfamily. Recent studies provide substantial evidence for MAP4K family kinases in the Hippo pathway regulation, suggesting a broad role of MAP4Ks in human physiology and diseases. However, a comprehensive analysis of the regulators and effectors for this key kinase family has not been fully achieved. Using a proteomic approach, we define the protein-protein interaction network for human MAP4K family kinases and reveal diverse cellular signaling events involving this important kinase family. Through it, we identify a STRIPAK complex component, STRN4, as a generic binding partner for MAP4Ks and a key regulator of the Hippo pathway in endometrial cancer development. Taken together, the results of our study not only generate a rich resource for further characterizing human MAP4K family kinases in numerous biological processes but also dissect the STRIPAK-mediated regulation of MAP4Ks in the Hippo pathway.

BACKGROUND: Recent studies showed that aberrant expression of miRNAs causes tumor-suppressing or promoting effects in various cancers including gastric cancer (GC). Our previous studies showed that lots of miRNAs and mRNA expressed differentially in GC and normal tissues. However, the critical miRNAs and mRNA need to be clarified.
METHODS: Microarray sequencing was used to profile the differential expression of miRNAs and mRNA in GC and normal tissues. Bioinformatics analysis and database prediction were used to search the critical miRNAs and mRNA. Real-time quantitative polymerase chain reaction (RT-qPCR), luciferase reporter assay, immunohistochemistry (IHC), wound healing assay and transwell assay were used to clarify the relationship between the target miRNAs and mRNA. Statistical analysis was used to seek their value of diagnosis and prognosis.
RESULTS: We identified microRNA-6165 (miR-6165) as a novel cancer-related miRNA in GC through high-throughput microarray sequencing. By bioinformatics analysis and luciferase reporter assay, we found STRN4 was the target of miR-6165. Via a series of cell experiments, we determined that miR-6165 suppressed GC cells migration and invasion by targeting STRN4. Also, we discovered the potential diagnosis and prognosis value of miR-6165 and STRN4.
CONCLUSIONS: It was found that miR-6165 might suppress GC migration and invasion by targeting STRN4 in vitro, and the further research should focus more on the potential diagnosis and prognosis value of miR-6165 and STRN4 in gastric cancer patients.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high fatality, low overall cure, and survival rates worldwide. When only palliative therapy is available, the disease leads to malignant proliferation. Previous studies showed miR-29b serves as an NSCLC suppressor by inhibiting cells proliferation, migration, and invasion. However, the mechanism underlying NSCLC progression remains elusive. In this study, we identified Striatin 4 (STRN4), a target of miR-29b, which serves as a pro-oncogenic protein by promoting cells proliferation, migration, and invasion in NSCLC. Besides, the STRN4 was highly expressed in NSCLC and negatively regulated by miR-29b. Down-regulation of STRN4 inhibits NSCLC cells proliferation, migration, invasion, and promotes apoptosis in vitro, whereas overexpression-induced enhanced cell migration and invasion could be reverved by miR-29b. Notably, overexpression of miR-29b and down-regulation of STRN4 by shRNA suppressed cellular proliferation and delayed tumor progression in vivo. Together, these findings identify a miR-29b/STRN4 regulatory pathway in NSCLC progression, which may provide a new sight for the treatment of NSCLC.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that directly bind to the 3\'-untranslated-region (3\'UTR) of mRNA, thereby blocking gene expression post-transcriptionally. Accumulating evidence prove that microRNA-873 (miR-873) functions as a promoter or suppressor in various cancers, while whether it affects the progression of colorectal cancer (CRC) is yet unknown. Here we found that miR-873 was downregulated in human CRC clinical samples, mouse CRC specimens and cell lines with high metastatic potential. We also demonstrated that low miR-873 expression was closely associated with poor prognosis of CRC. Overexpressing miR-873 suppressed proliferation and metastasis of CRC cells both in vitro and in vivo, while inhibiting miR-873 expression promoted the proliferation, migration and invasion in vitro. Moreover, miR-873 exerted its function by perturbing the ERK-CyclinD1 pathway and the epithelial-mesenchymal transition (EMT) process. Furthermore, we revealed that miR-873 acted as a tumor-suppressive microRNA by directly binding to the 3\'UTRs of ELK1 and STRN4 and suppressed their expression. Our study uncovered an inhibitory role of miR-873 in CRC progression and might provide a promising marker for CRC diagnosis and prognosis.

Pokemon, also known as leukemia/lymphoma-related factor (LRF) is a pro-oncogenic protein highly expressed in several cancers. There have been few in vitro and animal studies about its malignant biological behavior and function, however, its role especially in prostate cancer has not been completely elucidated. Therefore, in this study, we identified that Pokemon is overexpressed in human prostate cancer tissue samples, and its suppression inhibits proliferation of prostate cancer cells, along with promotion of apoptosis. Furthermore, to explore the mechanism by which Pokemon promotes tumor progression, we observed that it binds to the promoter of STRN4 (striatin 4), a downstream target, and subsequently regulates its expression. In conclusion, our study indicated that Pokemon through stimulation of STRN4 expression promotes prostate tumor progression via a Pokemon /STRN4 axis.

The striatin family of proteins, comprising STRN, STRN3 and STRN4, are multidomain-containing proteins that associate with additional proteins to form a large protein complex. We previously reported that STRN4 directly associated with protein kinases, such as MINK1, TNIK and MAP4K4, which are associated with tumor suppression or tumor progression. However, it remains unclear whether STRN4 is associated with tumor progression. In this report, we examined the role that STRN4 plays in cancer malignancy. We show that depletion of STRN4 suppresses proliferation, migration, invasion and the anchorage-independent growth of cancer cells. In addition, STRN4 knockdown increases the sensitivity of pancreatic cancer cells to gemcitabine. Finally, we show that STRN4 knockdown suppresses the proliferation and metastasis of cancer cells in mice. Our results demonstrate a possible role of STRN4 in tumor progression.