The LSM (Like-Sm) protein family, characterized by highly conserved LSM domains, is integral to ribonucleic acid (RNA) metabolism. Ubiquitously present in both eukaryotes and select prokaryotes, these proteins bind to RNA molecules with high specificity through their LSM domains. They can also form ring-shaped complexes with other proteins, thereby facilitating various fundamental cellular processes such as mRNA degradation, splicing, and ribosome biogenesis. LSM proteins play crucial roles in gametogenesis, early embryonic development, sex determination, gonadal maturation, and reproductive system formation. In pathological conditions, the absence of LSM14B leads to arrest of oocytes at mid-meiosis, downregulation of LSM4 expression is associated with abnormal spermatogenesis, and aberrant expression of LSM1 protein is linked to the occurrence and progression of breast cancer. This review focuses on the recent advances in the functional research of LSM proteins in reproduction.

Glioma, particularly glioblastoma (GBM), remains a highly aggressive and challenging tumour, characterised by poor prognosis and limited therapeutic options. LSM2, an RNA-binding protein, has been implicated in tumour progression, yet its role in glioma remains underexplored. This study aims to investigate the expression, prognostic significance, and molecular mechanisms of LSM2 in glioma, focusing on its impact on RNA splicing regulation.

Clinical and transcriptomic data from 163 GBM and 518 lower-grade glioma (LGG) cases from The Cancer Genome Atlas (TCGA) were analysed to assess LSM2 expression and its prognostic value. RNA sequencing was performed on LSM2 knockdown in T98G glioblastoma cells to identify differentially expressed genes (DEGs) and alternative splicing events (ASEs). Bioinformatics tools were employed to perform functional enrichment analyses and construct protein-protein interaction (PPI) networks.

LSM2 expression was significantly elevated in gliomas, particularly in GBM and in tumours with 1p/19q non-deletion or IDH1 mutation (p < 0.001). High LSM2 expression was correlated with shorter overall survival (HR = 1.7, p = 0.01). Knockdown of LSM2 in T98G cells identified 728 upregulated and 1,720 downregulated genes, alongside 1,949 splicing alterations, which primarily affected pathways related to RNA metabolism, DNA damage response, and cell cycle regulation. Key hub genes such as TLN1, FN1, and IRF7 were associated with glioma progression and poor prognosis.

Our findings demonstrate that LSM2 plays a critical role in glioma progression through the regulation of RNA splicing dynamics. Elevated LSM2 expression serves as a prognostic biomarker and offers promising potential as a therapeutic target in glioma.

The Musashi family of sequence-specific RNA binding proteins (Musashi1 and Musashi2) serve a critical role in mediating both physiological and pathological stem cell function in many tissue types by repressing the translation of target mRNAs that encode proteins that promote cell cycle inhibition and cell differentiation. In addition to repression of target mRNAs, we have also identified a role for Musashi proteins in activating the translation of target mRNAs in a context-dependent manner. However, the molecular mechanisms by which Musashi controls target mRNA translational activation have not been fully elucidated. Since Musashi lacks inherent enzymatic activity, its ability to modulate target mRNA translation likely involves recruitment of ancillary proteins to the target mRNA. We have previously identified a number of proteins that specifically associate with Musashi during Xenopus laevis oocyte maturation at a time when Musashi target mRNAs are translationally activated. Here, we demonstrate that one of these proteins, the Scd6/Like-sm family member LSM14B, is a mediator of the Musashi1-dependent mRNA translational activation that is required for oocyte maturation. Unlike previously characterized proteins which interact with the C-terminal domain of Musashi, LSM14B instead associates with the N-terminal RNA recognition motifs. Additionally, we demonstrate that the mammalian Prop1 mRNA, which encodes a key regulator of pituitary development, is translationally activated by Musashi1 in a LSM14B-dependent manner. Our studies support an evolutionarily conserved role for LSM14B in facilitating the ability of Musashi1 to promote target mRNA translation.

Dysregulated RNA processing is crucial in nasopharyngeal carcinoma (NPC) progression. Our research aimed to evaluate the prognostic values of RNA-processing genes (RPGs) in NPC through bioinformatic analysis of the GSE12452 and GSE102349 datasets, identifying differentially expressed RNA-processing genes (DE-RPGs). A prognostic model was developed using univariate and multivariate Cox analysis, with effectiveness assessed by ROC analysis. The correlation between risk scores, immune characteristics, and chemotherapy sensitivity was also analyzed. Model gene expression was validated by RT-qPCR, Western Blot, and immunohistochemistry, alongside functional assays. Bioinformatics indicated that RNA binding motif protein 20 (RBM20) and LSM5 are prognostic RPGs, with the ROC curve confirming their predictive ability for survival. Significant differences in drug sensitivity were noted between high- and low-risk groups. Experimental validation showed LSM5 is overexpressed in NPC tissues, correlating with poorer prognosis, and its down-regulation inhibits cell proliferation and migration. Thus, LSM5 is identified as a new adverse biomarker in NPC, with implications for targeted therapy and prognosis improvement.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the swine industry worldwide. Despite numerous studies on this virus, the molecular mechanisms underlying PRRSV infection remain unclear. Enhancer of mRNA decapping 3 (EDC3) is a crucial scaffold protein for P-body assembly that stimulates mRNA decapping by alleviating self-inhibition of the DCP1/2 decapping complex. In this study, we investigated the impact of EDC3 on PRRSV proliferation, as well as its influence on three key adaptor proteins of the innate immune system: Toll-like receptor interleukin-1 receptor domain-containing adaptor inducing interferon-β (TRIF), mitochondrial antiviral signaling protein (MAVs), and myeloid differentiation factor 88 (MyD88). Western blotting and quantitative real-time PCR assays showed that EDC3 overexpression in both Marc-145 and PAM-CD163 cells significantly inhibited transcription of the PRRSV N gene and expression of the N protein. Conversely, knockdown of EDC3 expression in these cells significantly promoted the transcription of the PRRSV N gene and expression of the N protein. Furthermore, our results demonstrated that EDC3 overexpression significantly enhanced the expression of MyD88, whereas the inhibition of EDC3 expression led to a reduction in this process. In contrast, EDC3 did not effectively promote the increase in protein levels of TRIF and MAVs. In conclusion, the P-body EDC3 protein suppresses PRRSV proliferation and function by upregulating MyD88. This work is the first to report the mechanism of action of EDC3 against PRRSV, providing ideas for studying antiviral innate immunity.

Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.

Glioblastoma (GBM) is characterized by aggressive growth, invasiveness, and poor prognosis. Elucidating the molecular mechanisms underlying GBM is crucial. This study explores the role of Sm-like protein 14 homolog A (LSM14A) in GBM. Bioinformatics and clinical tissue samples analysis demonstrated that overexpression of LSM14A in GBM correlates with poorer prognosis. CCK8, EdU, colony formation, and transwell assays revealed that LSM14A promotes proliferation, migration, and invasion in GBM in vitro. In vivo mouse xenograft models confirmed the results of the in vitro experiments. The mechanism of LSM14A modulating GBM cell proliferation was investigated using mass spectrometry, co-immunoprecipitation (coIP), protein half-life, and methylated RNA immunoprecipitation (MeRIP) analyses. The findings indicate that during the G1/S phase, LSM14A stabilizes DDX5 in the cytoplasm, regulating CDK4 and P21 levels. Furthermore, METTL1 modulates LSM14A expression via mRNA m7G methylation. Altogether, our work highlights the METTL1-LSM14A-DDX5 pathway as a potential therapeutic target in GBM.

The role of Sm-like 5 (LSM5) in colon cancer has not been determined. In this study, we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism involved.

To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism involved.

The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis analysis. Real-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins. A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 expression. Proliferation and apoptosis assays were also conducted to evaluate the growth of the colon cancer cells. Human GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon cancer.

LSM5 was highly expressed in tumor tissue and colon cancer cells. A high expression level of LSM5 was related to poor prognosis in patients with colon cancer. Knockdown of LSM5 suppressed proliferation and promoted apoptosis in colon cancer cells. Silencing of LSM5 also facilitates the expression of p53, cyclin-dependent kinase inhibitor 1A (CDKN1A) and tumor necrosis factor receptor superfamily 10B (TNFRSF10B). The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53, CDKN1A and TNFRSF10B.

LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53, CDKN1A and TNFRSF10B.

Hepatocellular carcinoma (HCC) is one of the most significant causes of cancer-related deaths in the worldwide. Currently, predicting the survival of patients with HCC and developing treatment drugs still remain a significant challenge. In this study, we employed prognosis-related genes to develop and externally validate a predictive risk model. Furthermore, the correlation between signaling pathways, immune cell infiltration, immunotherapy response, drug sensitivity, and risk score was investigated using different algorithm platforms in HCC. Our results showed that 11 differentially expressed genes including UBE2C, PTTG1, TOP2A, SPP1, FCN3, SLC22A1, ADH4, CYP2C8, SLC10A1, F9, and FBP1 were identified as being related to prognosis, which were integrated to construct a prediction model. Our model could accurately predict patients' overall survival using both internal and external datasets. Moreover, a strong correlation was revealed between the signaling pathway, immune cell infiltration, immunotherapy response, and risk score. Importantly, a novel potential drug candidate for HCC treatment was discovered based on the risk score and also validated through ex vivo experiments. Our finds offer a novel perspective on prognosis prediction and drug exploration for cancer patients.

NAADP is one of the most potent calcium mobilizing second messengers. Only recently, two NAADP-binding proteins have been identified: HN1L/JPT2 and LSM12. Further, ASPDH was suggested as a less selective binding partner. Apart from this newly uncovered link, little is known about the shared mechanisms between these proteins. The aim of this review is to assess potential functional connections between NAADP and its binding proteins. We here give a description of two major links. For one, HN1L/JPT2 and LSM12 both have potent oncogenic functions in several cancer types. Second, they are involved in similar cellular pathways in both cancer and immunity.

The RNA polymerase III (Pol III) transcriptome is universally comprised of short, highly structured noncoding RNA (ncRNA). Through RNA-protein interactions, the Pol III transcriptome actuates functional activities ranging from nuclear gene regulation (7SK), splicing (U6, U6atac), and RNA maturation and stability (RMRP, RPPH1, Y RNA), to cytoplasmic protein targeting (7SL) and translation (tRNA, 5S rRNA). In higher eukaryotes, the Pol III transcriptome has expanded to include additional, recently evolved ncRNA species that effectively broaden the footprint of Pol III transcription to additional cellular activities. Newly evolved ncRNAs function as riboregulators of autophagy (vault), immune signaling cascades (nc886), and translation (Alu, BC200, snaR). Notably, upregulation of Pol III transcription is frequently observed in cancer, and multiple ncRNA species are linked to both cancer progression and poor survival outcomes among cancer patients. In this review, we outline the basic features and functions of the Pol III transcriptome, and the evidence for dysregulation and dysfunction for each ncRNA in cancer. When taken together, recurrent patterns emerge, ranging from shared functional motifs that include molecular scaffolding and protein sequestration, overlapping protein interactions, and immunostimulatory activities, to the biogenesis of analogous small RNA fragments and noncanonical miRNAs, augmenting the function of the Pol III transcriptome and further broadening its role in cancer. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Processing of Small RNAs RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Comprehensive analysis of the expression and probable function of LSM2 in Live hepatocellular carcinoma (LIHC), and validation via in vitro experiments. Integrated use of database resources to examine the differential expression, survival prognosis, clinicopathological characteristics, and functional enrichment of LSM2 in LIHC. The expression level of LSM2 in LIHC tissues and adjacent tissues was proven via immunohistochemical staining. The biological function of LSM2 in LIHC was detected by cell proliferation, cell cloning, cell scratch, cell migration, and invasion experiments in vitro. TIMER 2.0 and GEPIA indicated that LSM2 was highly expressed in cancers and was strongly associated with survival rates in LIHC, cholangiocarcinoma, breast cancer, and renal clear cell carcinoma. LSM2 was highly expressed in LIHC, which was closely associated to the clinicopathological characteristics of patients, and the overall survival rate and disease-free survival rate of patients with high expression of LSM2 were lower than those with low expression of LSM2. Functional enrichment results revealed that LSM2 was involved to ribosome formation, DNA replication, cell cycle, metabolic processes, JAK-STAT signaling pathways, and FoxO signaling pathways. Knockdown of LSM2 inhibited the proliferation, migration, and invasion of LIHC cells in vitro experiments. LSM2 was highly expressed in LIHC and was related to a poor prognosis. Knockdown of LSM2 could inhibit the proliferation, migration, and invasion of LIHC cells.

Skin cutaneous melanoma (SKCM) is an extremely malignant tumor that is associated with a poor prognosis. LSM2 has been found to be related to different types of tumors; however, its role in SKCM is poorly defined. We aimed to determine the value of LSM2 as a prognostic biomarker for SKCM.

The expression profile of LSM2 mRNA was compared between tumor and normal tissues in public databases, such as TCGA, GEO, and BioGPS. LSM2 protein expression was explored using immunohistochemistry (IHC) on a tissue microarray containing 44 SKCM tissues and 8 normal samples collected at our center. Kaplan-Meier analysis was performed to assess the prognostic value of LSM2 expression in patients with SKCM. SKCM cell lines with LSM2 knockdown were used to determine the effects of LSM2. Cell counting kit-8 (CCK8) and colony formation assays were conducted to assess cell proliferation, whereas wound healing and transwell assays were carried out to assess the migration and invasion abilities of SKCM cells.

LSM2 was more highly expressed at the mRNA and protein levels in SKCM than that in normal skin. Moreover, elevated expression of LSM2 was associated with shorter survival time and early recurrence in patients with SKCM. The in vitro results revealed that the silencing of LSM2 in SKCM cells significantly inhibited cell proliferation, migration, and invasion.

Overall, LSM2 contributes to malignant status and poor prognosis in patients with SKCM and may be identified as a novel prognostic biomarker and therapeutic target.

Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer (CRC), but the molecular mechanism is still unclear. Recently, RNA-splicing factor LSM12 (like-Sm protein 12) is highly expressed in CRC tissues. This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway. Here, we found that LSM12 is highly expressed in CRC patient-derived tissues and cells. LSM12 is involved in the proliferation, invasion, and apoptosis of CRC cells, similar to the function of WNT signaling in CRC. Furthermore, protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1 (also known as β-Catenin) and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway. LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis. Taken together, we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation, and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.

Screening cancer genomes has provided an in-depth characterization of genetic variants such as copy number variations (CNVs) and gene expression changes of non-coding transcripts. Single-dimensional experiments are often designed to differentiate a patient cohort into various sets with the aim of identifying molecular changes among groups; however, this may be inadequate to decipher the causal relationship between molecular signatures in individual patients. To overcome this challenge with respect to personalized medicine, we implemented a patient-specific multi-dimensional integrative approach to uncover coherent signals from multiple independent platforms. In particular, we focused on the consistent gene dosage effects of CNVs for both mRNA and long non-coding RNA (lncRNA) expression in nine colorectal cancer patients. We identified 511 CNV-lncRNA-mRNA regulatory triplets associated with CNVs and aberrant expression of both mRNAs and lncRNAs. By filtering out inconsistent changes among CNVs, mRNAs, and lncRNAs, we further characterized 165 coherent motifs associated with 56 genes. In total, 108 motifs were linked with 31 copy number gains, 44 upregulated lncRNAs, and 45 upregulated mRNAs. Another 57 coherent downregulated motifs were also collected. We discuss how for many of these CNV-lncRNA-mRNA regulatory triplets, their clinical impact remains to be explored, including survival time, microsatellite instability, tumor stage, and primary tumor sites. By validating two example CNV-lncRNA-mRNA triplets with up- and down-regulation, we confirmed that individual variations in multiple dimensions are a robust tool to identify reliable molecular signals for personalized medicine. In summary, we utilized a patient-specific computational pipeline to explore the consistent CNV-driven motifs consisting of lncRNAs and mRNAs. We also identified LSM14B as a potential promoter in colorectal cancer progression, suggesting that it may serve as a target for colorectal cancer treatment.