CircRNA-regulated glucose metabolism in ovarian cancer: an emerging landscape for therapeutic intervention

Ovarian cancer (OC) has the highest mortality rate among female reproductive system tumours, with limited efficacy of traditional treatments and 5-year survival rates that rarely exceed 40%. Circular RNA (circRNA) is a stable endogenous circular RNA that typically regulates protein expression by binding to downstream miRNA. It has been demonstrated that circRNAs play an important role in the proliferation, migration, and glucose metabolism (such as the Warburg effect) of OC and can regulate the expression of glucose metabolism-related proteins such as GLUT1 and HK2, promoting anaerobic glycolysis of cancer cells, increasing glucose uptake and ATP production, and affecting energy supply and biosynthetic substances to support tumour growth and invasion. This review summarises the formation and characteristics of circRNAs and focuses on their role in regulating glucose metabolism in OC cells and their potential therapeutic value, providing insights for identifying new therapeutic targets (AU)

LncRNA XXYLT1-AS2 promotes tumor progression via autophagy inhibition through ubiquitinated degradation of TFEB in hepatocellular carcinoma

Purpose There is compelling evidence that long-stranded non-coding RNAs (lncRNAs) play an important role in the progression of hepatocellular carcinoma (HCC). The aim of this study was to investigate the role of lncRNA XXYLT1 antisense-2 (XXYLT1-AS2) in HCC progression. Methods Real-time PCR was used to assess the levels of XXYLT1-AS2 in plasma from HCC and normal patients. Cell proliferation, apoptosis, migration, and invasion were monitored, and tumor xenografts were established to investigate the biological functions of XXYLT1-AS2 by gain-of-function and loss-of-function studies in vitro and in vivo, the expression of autophagy biomarkers and transcriptional factor EB (TFEB) was examined by immunoprecipitation, ubiquitination assays, and western blotting. Autophagy inhibitor, 3-methyladenine (3MA), and proteasome inhibitor, MG132, were used to verify the role of autophagy in HCC progression and the effect of XXYLT1-AS2 on TFEB ubiquitination, respectively. Results In this study, we identified that lncRNA XXYLT1-AS2 is highly expressed in HCC plasma and promotes tumor growth in vivo. In functional studies, it was found that silent expression of XXYLT1-AS2 inhibited HCC proliferation, migration, invasion, and activated autophagy of HCC cells, which were attenuated by autophagy inhibitor, 3MA. Mechanistically, XXYLT1-AS2 decreased the protein level of TFEB through promoting its degradation by ubiquitin proteasome pathway. Conclusion XXYLT1-AS2 plays an oncogenic role in HCC progression through inhibition of autophagy via promoting the degradation of TFEB, and thus could be a novel target for HCC treatment (AU)

Glioblastoma research on zebrafish xenograft models: a systematic review

Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords “glioblastoma,” “xenotransplantation,” and “zebrafish” for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50–100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32–33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials (AU)

MicroRNA-128 acts as a suppressor in the progression of gastrointestinal stromal tumor by targeting B-lymphoma Mo-MLV insertion region 1

Introduction The critical role of microRNA-128 (miR-128) in gastrointestinal-related diseases has been documented. In the current study, we tried to clarify the specific role miR-128 in gastrointestinal stromal tumor (GIST) and the underlying mechanism. Methods Differentially expressed genes in GIST were identified following bioinformatics analysis. Then, expression patterns of miR-128 and B-lymphoma Mo-MLV insertion region 1 (BMI-1) in clinical tissue samples and cell lines were characterized, followed by validation of their correlation. GIST-T1 cells were selected and transfected with different mimic, inhibitor, or siRNA plasmids, after which the biological functions were assayed. Results We identified low miR-128 and high BMI-1 expression in GIST tissues of 78 patients and 4 GIST cell lines. Ectopic expression of miR-128 or silencing of BMI-1 suppressed the malignant potentials of GIST-T1 cells. As a target of miR-128, BMI-1 re-expression could partly counteract the suppressive effect of miR-128 on the malignancy of GIST-T1 cells. Conclusion Our study provided evidence that miR-128-mediated silencing of BMI-1 could prevent malignant progression of GIST, highlighting a promising anti-tumor target for combating GIST (AU)

LINC00844 suppresses tumor progression and predicts survival outcomes through inhibiting miR-19a-5p in cholangiocarcinoma

Background Cholangiocarcinoma (CCA) is a heterogeneous malignancy. The aim of the study was to investigate the regulatory role of long noncoding RNA LINC00844 in CCA progression, explore the underlying molecular mechanisms, and to analyze the potential prognostic value of LINC00844 in CCA patients. Methods Expression of LINC00844 in CCA cell lines and tissues was examined by reverse transcription-quantitative PCR. Cell counting kit-8 assay was used to assess CCA cell proliferation, and the Transwell assay was used to evaluate tumor cell migration and invasion. miRNAs sponged by LINC00844 were predicted and confirmed using a luciferase reporter assay. Kaplan–Meier survival analysis was performed to evaluate the survival prognosis of CCA patients. Results The expression levels of LINC00844 were decreased in CCA tissues and cells. Overexpression of LINC00844 inhibited cell proliferation, migration and invasion in CCA cells. miR-19a-5p is directly targeted by LINC00844, mediating the inhibitory effects of LINC00844 on the proliferation, migration and invasion of CCA cells. LINC00844 and miR-19a-5p expression were associated with differentiation and tumor node metastasis stage in CCA patients. CCA patients with low LINC00844 expression or overexpression of miR-19a-5p had worse overall survival. Conclusion The expression levels of LINC00844 were decreased in both CCA tissues and cells, and high LINC00844 inhibited CCA cell proliferation, migration and invasion through sponging miR-19a-5p. Low LINC00844 and high miR-19a-5p expression were associated with worse overall survival in CCA patients. All the data suggested that the LINC00844/miR-19a-5p axis may provide novel therapeutic targets and prognostic biomarkers for CCA patients (AU)

Role of miR-424 in the carcinogenesis

Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies (AU)

Carcinogenic roles of MAFG-AS1 in human cancers

The MAF bZIP transcription factor G-antisense RNA 1 (MAFG-AS1) is located on chromosome 17. MAFG-AS1 was upregulated in 15 human cancers. MAFG-AS1 not only suppresses 16 miRNAs but also directly impacts 22 protein-coding genes' expression. Notably, abnormal MAFG-AS1 expression is connected to clinicopathological characteristics and a worse prognosis in a variety of cancers. Moreover, MAFG-AS1 takes its part in the tumorigenesis and progression of various human malignancies by suppressing apoptosis and promoting proliferation, migration, invasion, aerobic glycolysis, ferroptosis, angiogenesis, EMT, and metastasis. Besides, it can predict treatment effectiveness in ER + breast cancer, urothelial bladder carcinoma, and liver cancer by functioning as a trigger of resistance to tamoxifen, sorafenib, and cisplatin. This study systematically presents the functions of MAFG-AS1 in various cancers, as well as the findings of bioinformatics analyses of the MAFG-AS1, which should give clear advice for future research (AU)

Delivery of SIRT1 by cancer-associated adipocyte-derived extracellular vesicles regulates immune response and tumorigenesis of ovarian cancer cells

Purpose This study intends to investigate the possible molecular mechanism of immune response and tumorigenesis in ovarian cancer cells, mediated by sirtuin 1 (SIRT1)-containing extracellular vesicles (EVs) derived from cancer-associated adipocytes (CAAs) (CAA-EVs). Methods Differentially expressed genes in EVs from CAAs were screened by RNA transcriptome sequencing, and the downstream pathway was predicted in silico. The binding between SIRT1 and CD24 was investigated by luciferase activity and ChIP-PCR assays. EVs were extracted from human ovarian cancer tissue-isolated CAAs, and the internalization of CCA-EVs by ovarian cancer cells was characterized. The ovarian cancer cell line was injected into mice to establish an animal model. Flow cytometry was performed to analyze the proportions of M1 and M2 macrophages, CD8+ T, T-reg, and CD4+ T cells. TUNEL staining was used to detect cell apoptosis in the mouse tumor tissues. ELISA detection was performed on immune-related factors in the serum of mice. Results CAA-EVs could deliver SIRT1 to ovarian cancer cells, thereby affecting the immune response of ovarian cancer cells in vitro and promoting tumorigenesis in vivo. SIRT1 could transcriptionally activate the expression of CD24, and CD24 could up-regulate Siglec-10 expression. CAA-EVs-SIRT1 activated the CD24/Siglec-10 axis and promoted CD8+ T cell apoptosis, thereby promoting tumorigenesis in mice. Conclusion CAA-EVs-mediated transfer of SIRT1 regulates the CD24/Siglec-10 axis to curb immune response and promote tumorigenesis of ovarian cancer cells (AU)

Synthesis of the scFv fragment of anti-Frizzled-7 antibody and evaluation of its effects on triple-negative breast cancer in vitro study

Objectives Among the most promising antibody formats in terms of inhibiting carcinogenesis are single-stranded variable fragments, whose targeted binding to the Fzd7 receptor has been proven effective at suppressing tumorigenesis. In this study, we investigated the effectiveness of an anti-Fzd7 antibody fragment against both tumor growth and metastasis of breast cancer cells. Methods To develop anti-Fzd7 antibodies, bioinformatics approaches were used and the antibodies were expressed recombinantly in E. coli BL21 (DE3). The expression of anti-Fzd7 fragments was verified by Western blotting. Analysis of the antibody's binding capacity to Fzd7 was conducted by flow cytometry. Cell death and apoptosis were assessed by MTT and Annexin V/PI assays. The transwell migration and invasion assays, as well as the scratch method, were used to evaluate cell motility and invasiveness. Results The anti-Fzd7 antibody was expressed successfully as a single band of 31 kDa. It could bind to 21.5% of MDA-MB-231 cells, as opposed to only 0.54% of SKBR-3 cells as negative control. According to MTT assay, induced apoptosis was 73.7% in MDA-MB-231 cells, compared with 29.5% in SKBR-3 cells. Also, the antibody exerted a significant inhibitory effect of 76% and 58% on migration and invasion of MDA-MB-231 cells, respectively. Conclusion The recombinantly developed anti-Fzd7 scFv of this study could exhibit significant antiproliferative and antimigratory properties, along with a high apoptosis-inducing potential, making it suitable for the immunotherapy of triple negative breast cancer (AU)

NPHS2-6 drives cervical squamous cell carcinoma (CSCC) progression via hsa-miR-1323/SMC1B axis to activate PI3K-Akt pathway

Purpose A substantial amount of evidence demonstrates suggests that long non-coding RNAs (lncRNAs) play a key role in the progression of various malignancies, cervical squamous cell carcinoma (CSCC) included. In our study, we deeply investigated the role and molecular mechanism of lncRNA NPHS2-6 in CSCC. Methods The expression level of gene and protein expression were measured by qRT-PCR and western blot. To test the cell proliferation and cell metastasis ability, we carried out the CCK-8 experiment, clone formation assay, transwell assay and wound healing, respectively. The interactivity among NPHS2-6, miR-1323 and SMC1B were co demonstrated using the bioinformatics tool, dual-luciferase reporter system, and RNA pulldown assay. The subcutaneous tumor model of nude mice was established to verify the results of previous studies at the in vivo. NPHS2-6 was upregulated in CSCC tissues and cells. Results NPHS2-6 deficiency significantly inhibited CSCC cell growth and EMT in vitro. In addition, NPHS2-6 deficiency also inhibited the growth of CSCC xenograft tumors in mice in vivo. Importantly, NPHS2-6 was a competing endogenous RNA (ceRNA) to increases SMC1B levels by binding to miR-1323, leading to activate the PI3K/Akt pathway, thereby exacerbating tumorigenesis of CSCC. Conclusions In conclusion, NPHS2-6/miR-1323/SMC1B/PI3K/Akt signaling accelerates the progression of CSCC, providing a new direction for the treatment strategy of CSCC (AU)

Single-cell RNA sequencing reveals the lineage of malignant epithelial cells and upregulation of TAGLN2 promotes peritoneal metastasis in gastric cancer

Background Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. Methods We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. Results Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial–mesenchymal transition (EMT). Conclusions In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination (AU)

Long noncoding RNA HOTAIR promotes breast cancer development through the lncRNA HOTAIR/miR-1/GOLPH3 axis

Background The lncRNA HOTAIR is frequently overexpressed in breast cancer tissues and plays an important role in the development of breast cancer. Here, we investigated the effect of the lncRNA HOTAIR on the biological behaviour of breast cancer cells and its molecular mechanism. Methods We investigated the level of HOTAIR in breast cancer and its clinical pathological characteristics by bioinformatic methods. Then, we evaluated the effects of HOTAIR and miRNA-1 expression on the biological behaviour of breast cancer cells by qPCR, Cell Counting Kit-8 (CCK-8) assay, clonogenic assays, Transwell assay and flow cytometry for cell proliferation, invasion migration and apoptosis, and cell cycle analysis. Finally, the target genes of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis were validated by luciferase reports. Results The expression of HOTAIR in breast cancer tissues was significantly higher than that in normal breast tissues (P < 0.05). Silencing of HOTAIR suppressed cell proliferation, invasion and migration, promoted apoptosis and induced G1 phase block in breast cancer (P < 0.0001). We also verified that miR-1 is a target of HOTAIR and that GOLPH3 is a target of miR-1 by luciferase reporter assays (P < 0.001). Conclusions The expression of HOTAIR was significantly elevated in breast cancer tissues. Reducing the expression of HOTAIR inhibited the proliferation, invasion and migration of breast cancer cells and promoted apoptosis, and the mechanism was mainly the effect of the lncRNA HOTAIR/miR-1/GOLPH3 regulatory axis on the biological behaviour of breast cancer cells (AU)

Effect of tumor exosome-derived Lnc RNA HOTAIR on the growth and metastasis of gastric cancer

Purpose HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC. Methods Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified. The expression levels of HOTAIR in GC cells, tissues, serum and serum exosomes were detected by fluorescence quantitative PCR (qRT-PCR), and the clinicopathological correlation was statistically analyzed. The growth and metastasis abilities of GC cells with HOTAIR knockdown in vitro were evaluated by cell experiment. The effects of HOTAIR highly-expressed NCI-N87 cell-derived exosomes were used to treat HOTAIR lowly-expressed MKN45 cells on GC growth and metastasis were also evaluated. Results The exosomes isolated by CD63-IMS had a particle size of 89.78 ± 4.8 nm and were oval membranous particles. The expression of HOTAIR in tumor tissues and serum of GC patients was increased (P < 0.05), and the expression of HOTAIR in serum exosomes was significantly increased (P < 0.01). The in NCI-N87 and MKN45 cell experiment demonstrated that HOTAIR knockdown by RNA interference suppressed cell growth and metastasis in NCI-N87 cells. Coculture of exosomes secreted by NCI-N87 cells with MKN45 cells significantly increased the expression of HOTAIR, and enhanced cell growth and metastasis. Conclusion LncRNA HOTAIR can be used as a potential biomarker which provides a new way for the diagnosis and treatment of GC (AU)

CISD2 promotes lung squamous carcinoma cell migration and invasion via the TGF-B1-induced Smad2/3 signaling pathway

Background Although aberrant expression of CDGSH iron sulfur domain 2 (CISD2) contributes to the tumorigenesis and progression of numerous human cancers, the biological function of CISD2 and its specific prognostic value in lung squamous cell carcinoma (LUSC) have yet to be comprehensively explored. The current study aimed to elucidate the role of CISD2 in LUSC as well as the underlying molecular mechanisms. Methods Immunohistochemistry was conducted to detect the protein expression of CISD2 and analyze whether high expression of CISD2 affects the overall survival (OS) of LUSC patients. Cell proliferation, colony formation, wound healing and Transwell invasion assays were performed to clarify whether CISD2 contributes to LUSC cell proliferation and disease progression. Quantitative real-time reverse transcription-PCR and western blot assays were used to detect the levels of transcription factors and key epithelial-mesenchymal transition (EMT)-related markers in LUSC cells after CISD2 knockdown and overexpression to determine whether CISD2 regulates transforming growth factor-beta (TGF-β)-induced EMT in LUSC. Results Immunohistochemistry of human tissue microarrays containing 90 pairs of adjacent and cancerous tissues revealed that CISD2 is considerably overexpressed in LUSC and strongly linked to poor OS. Functional experiments suggested that silencing endogenous CISD2 inhibited the growth, colony formation, migration, and invasion of H2170 and H226 cell lines. Exogenous overexpression of CISD2 facilitated these phenotypes in SK-MES-1 and H2170 cells. Furthermore, CISD2 promoted EMT progression by increasing the expression of mesenchymal markers (N-cadherin, vimentin, Snail, and Slug) as well as SMAD2/3 and reducing the expression of the epithelial marker E-cadherin. Mechanistically, our studies provide the first evidence that CISD2 can promote EMT by enhancing TGF-β1-induced Smad2/3 expression in LUSC cells (AU)

Induction of perineural invasion in salivary adenoid cystic carcinoma by circular RNA RNF111

Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)

LINC01119 encapsulated by cancer-associated adipocytes-derived exosomes promotes M2 polarization of macrophages to induce immune escape in ovarian cancer in a 3D co-culture cell-based model

Introduction In the present study, we sought to clarify the role of LINC01119 delivered by cancer-associated adipocytes (CAAs)-derived exosomes (CAA-Exo) and its mechanistic actions in ovarian cancer (OC). Materials and methods The expression of LINC01119 was determined in OC, and the relationship between LINC01119 expression and the prognosis of OC patients was analyzed. Besides, 3D co-culture cell models were constructed using green fluorescent protein-labeled OC cells and red fluorescent protein-labeled mature adipocytes. Mature adipocytes were co-cultured with OC cells to induce CAA. Macrophages treated with CAA-Exo were co-cultured with SKOV3 cells following ectopic expression and depletion experiments of LINC01119 and SOCS5 to detect M2 polarization of macrophages, PD-L1 level, proliferation of CD3+ T cells, and cytotoxicity of T cells to SKOV3 cells. Results LINC01119 was elevated in the plasma Exo of OC patients, which was related to shorter overall survival in OC patients. LINC01119 expression was increased in CAA-Exo, which could upregulate SOCS5 in OC. Finally, CAA-Exo carrying LINC01119 induced M2 polarization of macrophages to promote immune escape in OC, as evidenced by inhibited CD3+ T cell proliferation, increased PD-L1 level, and attenuated T cell toxicity to SKOV3 cells. Conclusion In conclusion, the key findings of the current study demonstrated the promoting effects of CAA-Exo containing LINC01119 mediating SOCS5 on M2 polarization of macrophages and immune escape in OC (AU)

LncRNA OTUD6B-AS1 overexpression promoted GPX4-mediated ferroptosis to suppress radioresistance in colorectal cancer

Background Radiotherapy is widely employed in colorectal cancer (CRC) treatment but is often compromised by developed radioresistance. This study explored the mechanism of long non-coding RNA ovarian tumor domain containing 6B-antisense RNA1 (lncRNA OTUD6B-AS1) in CRC radioresistance through tripartite motif 16 (TRIM16). Methods CRC and non-cancerous tissues were collected and radioresistant CRC cells were established, with real-time quantitative polymerase chain reaction to determine gene expression in tissues and cells. Radioresistance was evaluated by cell counting kit-8 assay and immunofluorescence (γ-H2AX) and ferroptosis was tested by Western blot assay (ACSL4/GPX4) and assay kits (Fe2+/ROS/MDA/GSH). The association between ferroptosis and lncRNA OTUD6B-AS1-inhibited radioresistance was testified using ferroptosis inhibitor. The subcellular localization of lncRNA OTUD6B-AS1 was tested by the nuclear/cytoplasmic fractionation assay, with RNA immunoprecipitation assay to validate gene interactions. Rescue experiments were conducted to analyze the role of TRIM16 in CRC radioresistance. Results LncRNA OTUD6B-AS1 and TRIM16 were poorly expressed (P < 0.01) in CRC tissues and cells and further decreased (P < 0.01) in radioresistant CRC cells. OTUD6B-AS1 overexpression decreased cell survival (P < 0.01), increased γ-H2AX levels (P < 0.01), and elevated ferroptosis and oxidative stress (P < 0.01) after X-ray radiation. Ferroptosis inhibitor attenuated radioresistance (P < 0.01) caused by lncRNA OTUD6B-AS1 overexpression. LncRNA OTUD6B-AS1 stabilized TRIM16 mRNA via binding to HuR. TRIM16 knockdown reduced ferroptosis and increased radioresistance (P < 0.05). Conclusion OTUD6B-AS1 overexpression stabilized TRIM16 via binding to HuR and increased GPX4-mediated ferroptosis, thus attenuating CRC radioresistance. Our study provided a new rationale for the treatment of CRC (AU)

Hsa_circ_0102899 promotes epithelial–mesenchymal transition in non-small cell lung cancer

Objective The significance of circular RNAs (circRNAs) has been identified in the progression of non-small cell lung cancer (NSCLC). Consistently, our study probed the functional actions of hsa_circ_0102899 (circ_0102899) in NSCLC cells. Methods circ_0102899 expression was checked in NSCLC tissues, as well as its correlation with clinical characteristics of patients, Using A459 cells, transfection to alter gene expression was performed, thus measuring the changes of proliferation, apoptosis, migration, and apoptosis, as well as epithelial–mesenchymal transition (EMT)-related proteins. circ_0102899’s effects in vivo were validated by tumor xenograft assay. Finally, the regulatory mechanism of circ_0102899 was investigated. Results circ_0102899 indicated a high-expression level in NSCLC tissues which was associated with NSCLC tumor characteristics. Functionally, circ_0102899 knockdown not only inhibited the growth and EMT process of NSCLC cells, but also inhibited tumor formation in vivo. In terms of the regulatory mechanism, circ_0102899 had a binding to miR-885-5p to target eukaryotic translation initiation factor 4γ2 (EIF4G2). circ_0102899 mediated miR-885–5/EIF4G2 axis to accelerate the process of cell malignant behavior in NSCLC. Conclusion circ_0102899 promotes EMT and metastasis in NSCLC by regulating the miR-885-5p/EIF4G2 axis (AU)

AKAP12 promotes cancer stem cell-like phenotypes and activates STAT3 in colorectal cancer

Background Cancer stem cells (CSCs) have unique biological characteristics, including tumorigenicity, immortality, and chemoresistance. Colorectal CSCs have been identified and isolated from colorectal cancers by various methods. AKAP12, a scaffolding protein, is considered to act as a potential suppressor in colorectal cancer, but its role in CSCs remains unknown. In this study, we investigated the function of AKAP12 in Colorectal CSCs. Methods Herein, Colorectal CSCs were enriched by cell culture with a serum-free medium. CSC-associated characteristics were evaluated by Flow cytometry assay and qPCR. AKAP12 gene expression was regulated by lentiviral transfection assay. The tumorigenicity of AKAP12 in vivo by constructing a tumor xenograft model. The related pathways were explored by qPCR and Western blot. Results The depletion of AKAP12 reduced colony formation, sphere formation, and expression of stem cell markers in colorectal cancer cells, while its knockdown decreased the volume and weight of tumor xenografts in vivo. AKAP12 expression levels also affected the expression of stemness markers associated with STAT3, potentially via regulating the expression of protein kinase C. Conclusion This study suggests Colorectal CSCs overexpress AKAP12 and maintain stem cell characteristics through the AKAP12/PKC/STAT3 pathway. AKAP12 may be an important therapeutic target for blocking the development of colorectal cancer in the field of cancer stem cells (AU)

Alternaria alternata (SDHY01/02), a fungus associated with Lamellodysidea herbacea: its anticancer potential and responsible constituent(s) / Alternaria alternata (SDHY01/02), un hongo asociado con Lamellodysidea herbacea: su potencial anticancerígeno y sus componentes responsables

One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC50 ≤ 20 µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC50 values ≤ 20 µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC50 values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC50 4.27 µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternata can be exploited to get anticancer molecule(s) in the future.(AU)