Cephalomannine reduces radiotherapy resistance in non-small cell lung cancer cells by blocking the ß-catenin-BMP2 signaling pathway.

BACKGROUND: The management of non-small cell lung cancer (NSCLC) often includes the use of radiotherapy, with individual outcomes being impacted by the tumor's response to this treatment modality. Cephalomannine (CPM), a taxane diterpenoid found in Taxus spp, has been found to have anti-tumor activity. This study was aim to the explore the role and mechanism by which CPM affects radiotherapy resistance in NSCLC. METHODS: H460 cells were pretreated with different doses of CPM. H460 cells were transfected with ß-catenin overexpression plasmids. The cell viability, colony-forming ability, migration ability, and sphere-forming ability and apoptosis of the cells were measured by using CCK-8, colony-forming, transwell, and sphere-forming assay and flow cytometry. Western blot assay was employed to detect the expression of ß-catenin and BMP2. RESULTS: The cell viability, proliferation, migration and sphere-forming ability of cells in the radiotherapy-resistant (RR) group were significantly higher than those in the radiotherapy-sensitivity (RS) group. Conversely, the apoptosis rate of cells in the RR group was lower than that in the RS group. However, after CPM pretreatment of RR group cells, the above phenomena were reversed in a CPM dose-dependent manner. Subsequently, pretreatment with CPM resulted in a decrease in the expression levels of ß-catenin and BMP2 in the RR group. In addition, overexpression of ß-catenin mitigated the inhibitory effects of CPM on radiotherapy-resistant NSCLC cells. CONCLUSION: CPM has the potential to decrease radiotherapy resistance in NSCLC cells by inhibiting the ß-catenin-BMP2 signaling pathway, promoting apoptosis, and ultimately impeding cell growth.

PRMT1 promotes radiotherapy resistance in glioma stem cells by inhibiting ferroptosis.

PURPOSE: The existence of glioma stem cells (GSCs) in cancer is related to glioma radiotherapy resistance. In this research, the effect of protein arginine methyltransferase 1 (PRMT1) on the radiosensitivity of glioma stem cell (GSC)-like cells, as well as its underlying mechanism, was investigated. METHODS: GSCs-like cells were analyzed and identified by flow cytometry. The self-renewal capability was evaluated by sphere-forming assay. The PRMT1 expression level in glioblastoma were analyzed using the Gene Expression Profiling Interactive Analysis database. The mRNA and protein were scrutinized by RT-qPCR and western blot, respectively. The radiosensitivity was evaluated by clonogenic survival assay. Ferroptosis was evaluated by detecting the levels of reactive oxygen species, malondialdehyde, Fe2+, glutathione, and 4-hydroxynonenal. RESULTS: U87 and SHG44 cells with GSC-like phenotype (GSC-U87 and GSC-SHG44) displayed strong expression of CD133 and nestin versus the glioma cells. GSC-U87 and GSC-SHG44 possess the self-renewal capability. The level of PRMT1 was higher in glioblastoma tumor tissues than in the normal paracancer tissues. Knockdown of PRMT1 enhanced the radiotherapy sensitivity of GSCs-like cells, which was evidenced by reduced survival fraction in GSC-U87 and GSC-SHG44 underwent sh-PRMT1 transfection. But, this effect was attenuated by Fer-1 (a ferroptosis inhibitor) treatment, accompanied by the abatement of ferroptosis. CONCLUSION: PRMT1 promoted radiotherapy resistance in GSCs-like cells by inhibiting ferroptosis.

Exposure to endocrine disruptor DEHP promotes the progression and radiotherapy resistance of pancreatic cancer cells by increasing BMI1 expression and properties of cancer stem cells.

Most patients diagnosed with pancreatic cancer are initially at an advanced stage, and radiotherapy resistance impact the effectiveness of treatment. This study aims to investigate the effects of endocrine disruptor Di-(2-ethylhexyl) phthalate (DEHP) on various biological behaviors and the radiotherapy sensitivity of pancreatic cancer cells, as well as its potential mechanisms. Our findings indicate that exposure to DEHP promotes the proliferation of various cancer cells, including those from the lung, breast, pancreas, and liver, in a time- and concentration-dependent manner. Furthermore, DEHP exposure could influence several biological behaviors of pancreatic cancer cells in vivo and vitro. These effects include reducing cell apoptosis, causing G0/G1 phase arrest, increasing migration capacity, enhancing tumorigenicity, elevating the proportion of cancer stem cells (CSCs), and upregulating expression levels of CSCs markers such as CD133 and BMI1. DEHP exposure can also increase radiation resistance, which can be reversed by downregulating BMI1 expression. In summary our research suggests that DEHP exposure can lead to pancreatic cancer progression and radiotherapy resistance, and the mechanism may be related to the upregulation of BMI1 expression, which leads to the increase of CSCs properties.

Mediation of radiation-induced bystander effect and epigenetic modification: The role of exosomes in cancer radioresistance.

Exosomes are nano-sized extracellular vesicles produced by almost all mammalian cells. They play an important role in cell-to-cell communication by transferring biologically active molecules from the cell of origin to the recipient cells. Ionizing radiation influences exosome production and molecular cargo loading. In cancer management, ionizing radiation is a form of treatment that exerts its cancer cytotoxicity by induction of DNA damage and other alterations to the targeted tissue cells. However, normal bystander non-targeted cells may exhibit the effects of ionizing radiation, a phenomenon called radiation-induced bystander effect (RIBE). The mutual communication between the two groups of cells (targeted and non-targeted) via radiation-influenced exosomes enables the exchange of radiosensitive molecules. This facilitates indirect radiation exposure, leading, among other effects, to epigenetic remodeling and subsequent adaptation to radiation. This review discusses the role exosomes play in epigenetically induced radiotherapy resistance through the mediation of RIBE.

Polymorphism in the Hsa-miR-4274 seed region influences the expression of PEX5 and enhances radiotherapy resistance in colorectal cancer.

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized treatments. We previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation therapy. Hence, to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer (CRC), in this study, bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5 (PEX5) as a direct target of miR-4274. The miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA, which subsequently regulates PEX5 protein expression. The interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence. A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in vivo. The overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation (IR)-induced DNA damage by the Ku70/Ku80 complex in the nucleus. In addition, the enhanced expression of PEX5 is associated with increased IR-induced ferroptosis. Thus, targeting this mechanism might effectively increase the radiosensitivity of CRC. These findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy.

Mechanisms of traditional Chinese medicine overcoming of radiotherapy resistance in breast cancer.

Breast cancer stands as the most prevalent malignancy among women, with radiotherapy serving as a primary treatment modality. Despite radiotherapy, a subset of breast cancer patients experiences local recurrence, attributed to the intrinsic resistance of tumors to radiation. Therefore, there is a compelling need to explore novel approaches that can enhance cytotoxic effects through alternative mechanisms. Traditional Chinese Medicine (TCM) and its active constituents exhibit diverse pharmacological actions, including anti-tumor effects, offering extensive possibilities to identify effective components capable of overcoming radiotherapy resistance. This review delineates the mechanisms underlying radiotherapy resistance in breast cancer, along with potential candidate Chinese herbal medicines that may sensitize breast cancer cells to radiotherapy. The exploration of such herbal interventions holds promise for improving therapeutic outcomes in the context of breast cancer radiotherapy resistance.

Molecular separation-assisted label-free SERS combined with machine learning for nasopharyngeal cancer screening and radiotherapy resistance prediction.

Nasopharyngeal cancer (NPC) is a malignant tumor with high prevalence in Southeast Asia and highly invasive and metastatic characteristics. Radiotherapy is the primary strategy for NPC treatment, however there is still lack of effect method for predicting the radioresistance that is the main reason for treatment failure. Herein, the molecular profiles of patient plasma from NPC with radiotherapy sensitivity and resistance groups as well as healthy group, respectively, were explored by label-free surface enhanced Raman spectroscopy (SERS) based on surface plasmon resonance for the first time. Especially, the components with different molecular weight sizes were analyzed via the separation process, helping to avoid the possible missing of diagnostic information due to the competitive adsorption. Following that, robust machine learning algorithm based on principal component analysis and linear discriminant analysis (PCA-LDA) was employed to extract the feature of blood-SERS data and establish an effective predictive model with the accuracy of 96.7% for identifying the radiotherapy resistance subjects from sensitivity ones, and 100% for identifying the NPC subjects from healthy ones. This work demonstrates the potential of molecular separation-assisted label-free SERS combined with machine learning for NPC screening and treatment strategy guidance in clinical scenario.

[Overexpression of ubiquitin-conjugating enzyme 2T induces radiotherapy resistance in hepatocellular carcinoma by enriching regulatory T cells in the tumor microenvironment].

OBJECTIVE: To investigate the effect of overexpression of ubiquitin-conjugating enzyme 2T (UBE2T) on radiosensitivity of hepatocellular carcinoma (HCC). METHODS: Hepa1-6 cells were transfected with a UBE2T-overexpressing or a control lentiviral vector, and the changes in their radiotherapy sensitivity and concentrations of glucose and lactate in the supernatant were assessed using colony-forming assay and colorimetric assay. The transfected cells were inoculated subcutaneously in nude mice or C57BL/6 mice, and tumor growth following irradiation were recorded. The xenografts were collected for analyzing infiltration of CD4+ T cells and regulatory T cells (Tregs) using flow cytometry and detecting expressions of HK1 and LDHA using Western blotting. The correlations of UBE2T expression with immune cell infiltration, glycolysis and Tregs in HCC were analyzed using CIBERSORT algorithm and TCGA database, and the results were verified in a co-culture system of Hepa1-6 cells and Tregs. RESULTS: UBE2T overexpression caused radiotherapy resistance in both cultured Hepa1-6 cells and xenografts in the tumor-bearing mouse models (especially in C57BL/6 mice). CIBERSORT analysis suggested that a high expression of UBE2T was associated with increased percentages of dendritic cells, T follicular helper cells, M2 macrophages, monocytes, lymphocytes and Tregs in HCC. The UBE2T-overexpressing xenografts showed an increased percentage of Tregs and enhanced expressions of HK1 and LDHA, and irradiation increased infiltration of CD4+ T cells and Tregs in the tumor microenvironment. Hepa1-6 cells overexpressing UBE2T showed a decreased glucose concentration and an increased lactate concentration. GSEA analysis suggested that a high UBE2T expression was positively correlated with increased glycolysis and Tregs infiltration in HCC. In the cell co-culture system, UBE2T overexpression significantly enhanced lactate production, proliferation and immunosuppressive functions of Tregs. CONCLUSION: A high UBE2T expression results in radiotherapy resistance of HCC possibly by enhancing glycolysis and cause enrichment of Tregs in the tumor microenvironment.

Current status and prospect of the DNA double-strand break repair pathway in colorectal cancer development and treatment.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Double-strand break (DSB) is the most severe type of DNA damage. However, few reviews have thoroughly examined the involvement of DSB in CRC. Latest researches demonstrated that DSB repair plays an important role in CRC. For example, DSB-related genes such as BRCA1, Ku-70 and DNA polymerase theta (POLQ) are associated with the occurrence of CRC, and POLQ even showed to affect the prognosis and resistance for radiotherapy in CRC. This review comprehensively summarizes the DSB role in CRC, explores the mechanisms and discusses the association with CRC treatment. Four pathways for DSB have been demonstrated. 1. Nonhomologous end joining (NHEJ) is the major pathway. Its core genes including Ku70 and Ku80 bind to broken ends and recruit repair factors to form a complex that mediates the connection of DNA breaks. 2. Homologous recombination (HR) is another important pathway. Its key genes including BRCA1 and BRCA2 are involved in finding, pairing, and joining broken ends, and ensure the restoration of breaks in a normal double-stranded DNA structure. 3. Single-strand annealing (SSA) pathway, and 4. POLθ-mediated end-joining (alt-EJ) is a backup pathway. This paper elucidates roles of the DSB repair pathways in CRC, which could contribute to the development of potential new treatment approaches and provide new opportunities for CRC treatment and more individualized treatment options based on therapeutic strategies targeting these DNA repair pathways.

The Role of αvß3 Integrin in Cancer Therapy Resistance.

A relevant challenge for the treatment of patients with neoplasia is the development of resistance to chemo-, immune-, and radiotherapies. Although the causes of therapy resistance are poorly understood, evidence suggests it relies on compensatory mechanisms that cells develop to replace specific intracellular signaling that should be inactive after pharmacological inhibition. One such mechanism involves integrins, membrane receptors that connect cells to the extracellular matrix and have a crucial role in cell migration. The blockage of one specific type of integrin is frequently compensated by the overexpression of another integrin dimer, generally supporting cell adhesion and migration. In particular, integrin αvß3 is a key receptor involved in tumor resistance to treatments with tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiotherapy; however, the specific inhibition of the αvß3 integrin is not enough to avoid tumor relapse. Here, we review the role of integrin αvß3 in tumor resistance to therapy and the mechanisms that have been proposed thus far. Despite our focus on the αvß3 integrin, it is important to note that other integrins have also been implicated in drug resistance and that the collaborative action between these receptors should not be neglected.

Transcription factor STAT4 counteracts radiotherapy resistance in breast carcinoma cells by activating the MALAT1/miR-21-5p/THRB regulatory network.

Considering the limited research and the prevailing evidence of STAT4's tumor-suppressing role in breast carcinoma (BC) or in breast radiotherapy (RT) sensitivity requires more in-depth exploration. Our study delves into how STAT4, a transcription factor, affects BC cell resistance to radiotherapy by regulating the MALAT1/miR-21-5p/THRB axis. Bioinformatics analysis was performed to predict the regulatory mechanisms associated with STAT4 in BC. Subsequently, we identified the expression profiles of STAT4, MALAT1, miR-21-5p, and THRB in various tissues and cell lines, exploring their interactions and impact on RT resistance in BC cells. Moreover, animal models were established with X-ray irradiation for further validation. We discovered that STAT4, which is found to be minimally expressed in breast carcinoma (BC) tissues and cell lines, has been associated with a poorer prognosis. In vitro cellular assays indicated that STAT4 could mitigate radiotherapy resistance in BC cells by transcriptional activation of MALAT1. Additionally, MALAT1 up-regulated THRB expression by adsorbing miR-21-5p. As demonstrated in vitro and in vivo, overexpressing STAT4 inhibited miR-21-5p and enhanced THRB levels through transcriptional activation of MALAT1, which ultimately contributes to the reversal of radiotherapy resistance in BC cells and the suppression of tumor formation in nude mice. Collectively, STAT4 could inhibit miR-21-5p and up-regulate THRB expression through transcriptional activation of MALAT1, thereby mitigating BC cell resistance to radiotherapy and ultimately preventing BC development and progression.

Pancreatic cancer cells hijack tumor suppressive microRNA-26a to promote radioresistance and potentiate tumor repopulation.

Pancreatic cancer is one of the most lethal cancers with significant radioresistance and tumor repopulation after radiotherapy. As a type of short non-coding RNA that regulate various biological and pathological processes, miRNAs might play vital role in radioresistance. We found by miRNA sequencing that microRNA-26a (miR-26a) was upregulated in pancreatic cancer cells after radiation, and returned to normal state after a certain time. miR-26a was defined as a tumor suppressive miRNA by conventional tumor biology experiments. However, transient upregulation of miR-26a after radiation significantly promoted radioresistance, while stable overexpression inhibited radioresistance, highlighting the importance of molecular dynamic changes after treatment. Mechanically, transient upregulation of miR-26a promoted cell cycle arrest and DNA damage repair to promote radioresistance. Further experiments confirmed HMGA2 as the direct functional target, which is an oncogene but enhances radiosensitivity. Moreover, PTGS2 was also the target of miR-26a, which might potentiate tumor repopulation via delaying the synthesis of PGE2. Overall, this study revealed that transient upregulation of miR-26a after radiation promoted radioresistance and potentiated tumor repopulation, highlighting the importance of dynamic changes of molecules upon radiotherapy.

CircCDYL2 bolsters radiotherapy resistance in nasopharyngeal carcinoma by promoting RAD51 translation initiation for enhanced homologous recombination repair.

BACKGROUND: Radiation therapy stands to be one of the primary approaches in the clinical treatment of malignant tumors. Nasopharyngeal Carcinoma, a malignancy predominantly treated with radiation therapy, provides an invaluable model for investigating the mechanisms underlying radiation therapy resistance in cancer. While some reports have suggested the involvement of circRNAs in modulating resistance to radiation therapy, the underpinning mechanisms remain unclear. METHODS: RT-qPCR and in situ hybridization were used to detect the expression level of circCDYL2 in nasopharyngeal carcinoma tissue samples. The effect of circCDYL2 on radiotherapy resistance in nasopharyngeal carcinoma was demonstrated by in vitro and in vivo functional experiments. The HR-GFP reporter assay determined that circCDYL2 affected homologous recombination repair. RNA pull down, RIP, western blotting, IF, and polysome profiling assays were used to verify that circCDYL2 promoted the translation of RAD51 by binding to EIF3D protein. RESULTS: We have identified circCDYL2 as highly expressed in nasopharyngeal carcinoma tissues, and it was closely associated with poor prognosis. In vitro and in vivo experiments demonstrate that circCDYL2 plays a pivotal role in promoting radiotherapy resistance in nasopharyngeal carcinoma. Our investigation unveils a specific mechanism by which circCDYL2, acting as a scaffold molecule, recruits eukaryotic translation initiation factor 3 subunit D protein (EIF3D) to the 5'-UTR of RAD51 mRNA, a crucial component of the DNA damage repair pathway to facilitate the initiation of RAD51 translation and enhance homologous recombination repair capability, and ultimately leads to radiotherapy resistance in nasopharyngeal carcinoma. CONCLUSIONS: These findings establish a novel role of the circCDYL2/EIF3D/RAD51 axis in nasopharyngeal carcinoma radiotherapy resistance. Our work not only sheds light on the underlying molecular mechanism but also highlights the potential of circCDYL2 as a therapeutic sensitization target and a promising prognostic molecular marker for nasopharyngeal carcinoma.

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer.

OBJECTIVE: Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. METHODS: The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models. RESULTS: Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway. CONCLUSION: High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.

Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway.

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.

Bioinspired Lipoproteins of Furoxans-Gemcitabine Preferentially Targets Glioblastoma and Overcomes Radiotherapy Resistance.

Radiotherapy (RT) resistance is an enormous challenge in glioblastoma multiforme (GBM) treatment, which is largely associated with DNA repair, poor distribution of reactive radicals in tumors, and limited delivery of radiosensitizers to the tumor sites. Inspired by the aberrant upregulation of RAD51 (a critical protein of DNA repair), scavenger receptor B type 1 (SR-B1), and C-C motif chemokine ligand 5 (CCL5) in GBM patients, a reduction-sensitive nitric oxide (NO) donor conjugate of gemcitabine (RAD51 inhibitor) (NG) is synthesized as radio-sensitizer and a CCL5 peptide-modified bioinspired lipoprotein system of NG (C-LNG) is rationally designed, aiming to preferentially target the tumor sites and overcome the RT resistance. C-LNG can preferentially accumulate at the orthotopic GBM tumor sites with considerable intratumor permeation, responsively release the gemcitabine and NO, and then generate abundant peroxynitrite (ONOO- ) upon X-ray radiation, thereby producing a 99.64% inhibition of tumor growth and a 71.44% survival rate at 120 days in GL261-induced orthotopic GBM tumor model. Therefore, the rationally designed bioinspired lipoprotein of NG provides an essential strategy to target GBM and overcome RT resistance.

Roles of long noncoding RNA in triple-negative breast cancer.

INTRODUCTION: Long noncoding RNAs (lncRNAs) play crucial roles in regulating various hallmarks in cancers. Triple-negative (Estrogen receptor, ER; Human epidermal growth factor receptor 2, HER2; Progesterone receptor, PR) breast cancer (TNBC) is the most aggressive form of breast cancers with a poor prognosis and no available molecular targeted therapy. METHODS: We reviewed the current literature on the roles of lncRNAs in the pathogenesis, therapy resistance, and prognosis of patients with TBNC. RESULTS: LncRNAs are associated with TNBC pathogenesis, therapy resistance, and prognosis. For example, lncRNAs such as small nucleolar RNA host gene 12 (SNHG12), highly upregulated in liver cancer (HULC) HOX transcript antisense intergenic RNA (HOTAIR), lincRNA-regulator of reprogramming (LincRNA-ROR), etc., are aberrantly expressed in TNBC and are involved in the pathogenesis of the disease. LncRNAs act as a decoy, scaffold, or sponge to regulate the expression of genes, miRNAs, and transcription factors associated with pathogenesis and progression of TNBC. Moreover, lncRNAs such as ferritin heavy chain 1 pseudogene 3 (FTH1P3), BMP/OP-responsive gene (BORG) contributes to the therapy resistance property of TNBC through activating ABCB1 (ATP-binding cassette subfamily B member 1) drug efflux pumps by increasing DNA repair capacity or by inducing signaling pathway involved in therapeutic resistance. CONCLUSION: In this review, we outline the functions of various lncRNAs along with their molecular mechanisms involved in the pathogenesis, therapeutic resistance of TBNC. Also, the prognostic implications of lncRNAs in patients with TNBC is illustrated. Moreover, potential strategies targeting lncRNAs against highly aggressive TNBC is discussed in this review.

RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma.

OBJECTIVES: RAD51 overexpression has been reported to serve as a marker of poor prognosis in several cancer types. This study aimed to survey the role of RAD51 in oral squamous cell carcinoma and whether RAD51 could be a potential therapeutic target. MATERIALS AND METHODS: RAD51 protein expression, assessed by immunohistochemical staining, was used to examine associations with survival and clinicopathological profiles of patients with oral squamous cell carcinoma. Lentiviral infection was used to knock down or overexpress RAD51. The influence of RAD51 on the biological profile of oral cancer cells was evaluated. Cell viability and apoptosis after treatment with chemotherapeutic agents and irradiation were analyzed. Co-treatment with chemotherapeutic agents and B02, a RAD51 inhibitor, was used to examine additional cytotoxic effects. RESULTS: Oral squamous cell carcinoma patients with higher RAD51 expression exhibited worse survival, especially those treated with adjuvant chemotherapy and radiotherapy. RAD51 overexpression promotes resistance to chemotherapy and radiotherapy in oral cancer cells in vitro. Higher tumorsphere formation ability was observed in RAD51 overexpressing oral cancer cells. However, the expression of oral cancer stem cell markers did not change in immunoblotting analysis. Co-treatment with RAD51 inhibitor B02 and cisplatin, compared with cisplatin alone, significantly enhanced cytotoxicity in oral cancer cells. CONCLUSION: RAD51 is a poor prognostic marker for oral squamous cell carcinoma. High RAD51 protein expression associates with resistance to chemotherapy and radiotherapy. Addition of B02 significantly increased the cytotoxicity of cisplatin. These findings suggest that RAD51 protein may function as a treatment target for oral cancer. TRIAL REGISTRATION: Number: KMUHIRB-E(I)-20190009 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, approved on 20190130, Retrospective registration.

Review of possible mechanisms of radiotherapy resistance in cervical cancer.

Radiotherapy is one of the main treatments for cervical cancer. Early cervical cancer is usually considered postoperative radiotherapy alone. Radiotherapy combined with cisplatin is the standard treatment for locally advanced cervical cancer (LACC), but sometimes the disease will relapse within a short time after the end of treatment. Tumor recurrence is usually related to the inherent radiation resistance of the tumor, mainly involving cell proliferation, apoptosis, DNA repair, tumor microenvironment, tumor metabolism, and stem cells. In the past few decades, the mechanism of radiotherapy resistance of cervical cancer has been extensively studied, but due to its complex process, the specific mechanism of radiotherapy resistance of cervical cancer is still not fully understood. In this review, we discuss the current status of radiotherapy resistance in cervical cancer and the possible mechanisms of radiotherapy resistance, and provide favorable therapeutic targets for improving radiotherapy sensitivity. In conclusion, this article describes the importance of understanding the pathway and target of radioresistance for cervical cancer to promote the development of effective radiotherapy sensitizers.