CircRNA SEC24A promotes osteoarthritis through miR-107-5p/CASP3 axis.

Background: Osteoarthritis (OA) is the most frequently diagnosed chronic joint disease. CircSEC24A is significantly elevated in OA chondrocytes upon IL-1ß stimulation. However, its biological function in OA is still not fully understood. Methods: The circRNAs-miRNA-mRNA network was predicted by bioinformatics analysis. An in vitro OA chondrocytes model was established by IL-1ß stimulation. The expression of circSEC24A, miR-107-5p, CASP3, apoptosis-related molecules and extracellular matrix (ECM) components were detected by Western blot and qRT-PCR. MTT assay and Annexin V/PI staining were employed to monitor cell viability and apoptosis, respectively. The interaction between circSEC24A and miR-107-5p, as well as the binding between miR-107-5p and CASP3 3' UTR were detected by luciferase reporter and RIP assays. Cytokine secretion was monitored by ELISA assay. The role of circSEC24A was also explored in anterior cruciate ligament transection (ACLT) rat models. Results: CircSEC24A and CASP3 were increased, but miR-107-5p was decreased in rat OA cartilage tissues and OA chondrocytes. CircSEC24A acted as a sponge of miR-107-5p. Knockdown of circSEC24A promoted chondrocyte proliferation, but suppressed chondrocyte apoptosis, ECM degradation and inflammation via sponging miR-107-5p. CASP3 was identified as a miR-107-5p target gene. MiR-107-5p mimics protected against OA progression via targeting CASP3. Silencing of circSEC24A alleviated OA progression in ACLT model. Conclusion: CircSEC24A promotes OA progression through miR-107-5p/CASP3 axis.

Isoflavones isolated from chickpea sprouts alleviate ovariectomy-induced osteoporosis in rats by dual regulation of bone remodeling.

Osteoporosis is a common systemic skeletal disease and a predominant underlying factor in the increased occurrence of fractures. The structure of isoflavones resembles that of estrogen and can confer similar but weaker effects. This study investigated the potential inhibitory effects of isoflavones from chickpea sprouts (ICS) on ovariectomy (OVX)-induced osteoporosis in vitro and in vivo. Notably, we found that ICS treatment could attenuate bone loss and improve trabecular microarchitecture and biomechanical properties of the fourth lumbar vertebra in OVX-induced osteoporotic rats and could also inhibit the development of a hyperosteometabolic state in this model. The osteogenic differentiation of bone marrow stem cells (BMSCs) was significantly enhanced by ICS intervention in vitro, and we confirmed that estrogen receptor α signaling was required for this increased osteogenic differentiation. Additionally, ICS has been shown to inhibit bone resorption via ERa modulation of the OPG/RANKL pathway. RANKL-induced osteoclastogenesis was reduced under ICS treatment, supporting that NF-κB signaling was inhibited by ICS. Thus, ICS attenuates osteoporosis progression by promoting osteogenic differentiation and inhibiting osteoclastic resorption. These results support the further exploration and development of ICS as a pharmacological agent for the treatment and prevention of osteoporosis.

Harnessing extremophilic carboxylesterases for applications in polyester depolymerisation and plastic waste recycling.

The steady growth in industrial production of synthetic plastics and their limited recycling have resulted in severe environmental pollution and contribute to global warming and oil depletion. Currently, there is an urgent need to develop efficient plastic recycling technologies to prevent further environmental pollution and recover chemical feedstocks for polymer re-synthesis and upcycling in a circular economy. Enzymatic depolymerization of synthetic polyesters by microbial carboxylesterases provides an attractive addition to existing mechanical and chemical recycling technologies due to enzyme specificity, low energy consumption, and mild reaction conditions. Carboxylesterases constitute a diverse group of serine-dependent hydrolases catalysing the cleavage and formation of ester bonds. However, the stability and hydrolytic activity of identified natural esterases towards synthetic polyesters are usually insufficient for applications in industrial polyester recycling. This necessitates further efforts on the discovery of robust enzymes, as well as protein engineering of natural enzymes for enhanced activity and stability. In this essay, we discuss the current knowledge of microbial carboxylesterases that degrade polyesters (polyesterases) with focus on polyethylene terephthalate (PET), which is one of the five major synthetic polymers. Then, we briefly review the recent progress in the discovery and protein engineering of microbial polyesterases, as well as developing enzyme cocktails and secreted protein expression for applications in the depolymerisation of polyester blends and mixed plastics. Future research aimed at the discovery of novel polyesterases from extreme environments and protein engineering for improved performance will aid developing efficient polyester recycling technologies for the circular plastics economy.

Mechanisms underlying the therapeutic effects of isoflavones isolated from chickpea sprouts in treating osteoporosis based on network pharmacology.

Osteoporosis is a systemic bone disease that is caused by multiple factors that lead to an imbalance in bone metabolism. Isoflavones can prevent and treat osteoporosis by regulating bone metabolism through a variety of pathways. The germination of chickpeas can significantly increase their isoflavone contents. However, the use of isoflavones isolated from chickpea sprouts (ICS) to prevent and treat osteoporosis by regulating bone metabolism has not been widely studied. In vivo experimental studies in ovariectomized rats showed that ICS significantly improved femoral bone mineral density (BMD) and trabecular structure, with effects similar to raloxifene. Furthermore, the chemical composition of ICS as well as the targets and signalling pathways its regulates in the prevention and treatment of osteoporosis were predicted by network pharmacological studies. ICS with drug-like properties were identified by Lipinski's 5 principles, and intersecting targets of isoflavones with osteoporosis were identified. The overlapping targets were analysed by PPI, GO and KEGG analyses, and the possible key targets, signalling pathways and biological processes by which ICS treats osteoporosis were predicted; the prediction results were verified by molecular docking technology. The results showed that ICS could play an important role in the treatment of osteoporosis through "multicomponent, multitarget and multipathway" mechanisms, and the MAKP, NF-kB and ER-related signalling pathways may be important pathways by which ICS regulates osteoporosis; these findings provide a new theoretical basis for further experimental studies.

SMALPs Are Not Simply Nanodiscs: The Polymer-to-Lipid Ratios of Fractionated SMALPs Underline Their Heterogeneous Nature.

Amphipathic styrene-maleic acid (SMA) copolymers directly solubilize biomembranes into SMA-lipid particles, or SMALPs, that are often regarded as nanodiscs and hailed as a native membrane platform. The promising outlook of SMALPs inspires the discovery of many SMA-like copolymers that also solubilize biomembranes into putative nanodiscs, but a fundamental question remains on how much the SMALPs or SMALP analogues truly resemble the bilayer structure of nanodiscs. This unfortunate ambiguity undermines the utility of SMA or SMA-like copolymers in membrane biology because the structure and function of many membrane proteins depend critically on their surrounding matrices. Here, we report the structural heterogeneity of SMALPs revealed through fractionating SMALPs comprised of lipids and well-defined SMAs via size-exclusion chromatography followed by quantitative determination of the polymer-to-lipid (P/L) stoichiometric ratios in individual fractions. Through the lens of P/L stoichiometric ratios, different self-assembled polymer-lipid nanostructures are inferred, such as polymer-remodeled liposomes, polymer-encased nanodiscs, polymer-lipid mixed micelles, and lipid-doped polymer micellar aggregates. We attribute the structural heterogeneity of SMALPs to the microstructure variations amongst individual polymer chains that give rise to their polydisperse detergency. As an example, we demonstrate that SMAs with a similar S/MA ratio but different chain sizes participate preferentially in different polymer-lipid nanostructures. We further demonstrate that proteorhodopsin, a light-driven proton pump solubilized within the same SMALPs is distributed amongst different self-assembled nanostructures to display different photocycle kinetics. Our discovery challenges the native nanodisc notion of SMALPs or SMALP analogues and highlights the necessity to separate and identify the structurally dissimilar polymer-lipid particles in membrane biology studies.

Serum D-lactate, a novel serological biomarker, is promising for the diagnosis of periprosthetic joint infection.

BACKGROUND: Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI. METHODS: Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values. RESULTS: Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively). CONCLUSION: Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.

Effects of intra-articular D-amino acids combined with systemic vancomycin on an experimental Staphylococcus aureus-induced periprosthetic joint infection.

BACKGROUND: The D-isoforms of amino acids (D-AAs) exhibit anti-biofilm potential against a diverse range of bacterial species in vitro, while its role in vivo remains unclear. The aim of this study was to investigate the effects of a combination of D-AAs and vancomycin on a PJI rat model. METHODS: Eight-week-old male SD rats were randomized to the control group, sham group, vancomycin group, D-AAs-vancomycin group. After treatment for 6 weeks, we analysed the levels of inflammatory factors in serum, behavioural change, imaging manifestations. The anti-biofilm ability of D-AAs was detected by crystal violet staining and scanning electron microscope observation, and its ability to assist antibiotics in killing bacteria was assessed by culture of bacteria. Additionally, micro-CT and histological analysis were used to evaluate the impact of D-AAs combined with vancomycin on the bone remodelling around the prosthesis. RESULTS: The group treated with a D-AAs-vancomycin combination sustained normal weight gain and exhibited reduced the serum levels of α2M, IL-1ß, IL-6, IL-10, TNF-α and PGE2. Moreover, treated with D-AAs in combination with vancomycin improved the weight-bearing activity performance, increased the sizes and widths of distal femurs, and improved Rissing scale scoring. In particular, treatment using D-AAs enhanced the ability of vancomycin to eradicate Staphylococcus aureus, as demonstrated by the dispersion of existing biofilms and the inhibition of biofilm formation that occurred in a concentration-dependent manner. This treatment combination also resulted in a reduction in bacterial burden with in the soft tissues, bones, and implants. Furthermore, D-AAs-vancomycin combination treatment attenuated abnormal bone remodelling around the implant, as evidenced by an observed increase in BMD, BV/TV, and Tb.Th and the presence of reduced Trap+ osteoclasts and elevated osterix+ osteo-progenitors. CONCLUSIONS: Combining D-AAs with vancomycin provides an effective therapeutic strategy for the treatment of PJI by promoting biofilm dispersion to enhance antimicrobial activity.

Nanodiscs: a versatile nanocarrier platform for cancer diagnosis and treatment.

Cancer therapy is a significant challenge due to insufficient drug delivery to the cancer cells and non-selective killing of healthy cells by most chemotherapy agents. Nano-formulations have shown great promise for targeted drug delivery with improved efficiency. The shape and size of nanocarriers significantly affect their transport inside the body and internalization into the cancer cells. Non-spherical nanoparticles have shown prolonged blood circulation half-lives and higher cellular internalization frequency than spherical ones. Nanodiscs are desirable nano-formulations that demonstrate enhanced anisotropic character and versatile functionalization potential. Here, we review the recent development of theranostic nanodiscs for cancer mitigation ranging from traditional lipid nanodiscs encased by membrane scaffold proteins to newer nanodiscs where either the membrane scaffold proteins or the lipid bilayers themselves are replaced with their synthetic analogues. We first discuss early cancer detection enabled by nanodiscs. We then explain different strategies that have been explored to carry a wide range of payloads for chemotherapy, cancer gene therapy, and cancer vaccines. Finally, we discuss recent progress on organic-inorganic hybrid nanodiscs and polymer nanodiscs that have the potential to overcome the inherent instability problem of lipid nanodiscs.

Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures.

To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn't alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (dsilica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells.

Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development.

Osteoarthritis (OA) is a degenerative joint disease with multiple etiologies that affects individuals worldwide. No effective interventions are currently available to reverse the pathological process of OA. Sodium butyrate (NaB), a component of short-chain fatty acids (SCFAs), has multiple biological activities, including the attenuation of inflammation and anti-tumor activities in various diseases. However, whether the protective effects of NaB in OA are associated with the promotion of autophagy had not been investigated. Here, we explored the chondroprotective properties of NaB in an interleukin (IL)-1ß-induced inflammatory chondrocyte model and an anterior cruciate ligament transection (ACLT) mouse model. Hematoxylin and eosin (HE), Safranin O, and immunohistochemical staining were performed to evaluate the effects of NaB treatment on articular cartilage. An optimal NaB dose for chondrocyte treatment was determined via cell counting kit-8 assays. Immunofluorescence and transmission electron microscopy were used to detect autophagy in chondrocytes. Flow cytometry was utilized to detect reactive oxygen species (ROS), cell cycle activity, and apoptosis in chondrocytes. Western blot and immunostaining were performed to evaluate the protein expression levels of relevant indicators. We found that the administration of NaB by oral gavage could attenuate cartilage degradation. In parallel, NaB treatment could enhance the activation of autophagy, increase autophagic flux, decrease extracellular matrix degradation, and reduce apoptosis by restraining inflammation, ROS production, and cell cycle arrest in IL-1ß-treated chondrocytes. The protective effects of NaB could be partially abolished by the autophagy inhibitor 3-methyladenine (3-MA), which indicated that the protective effects of NaB against OA were partially governed by the enhancement of autophagy to restrain the formation of inflammatory mediators and ROS and regulate cell cycle progression and apoptosis in chondrocytes. In conclusion, NaB could attenuate OA progression by restoring impaired autophagy and autophagic flux via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, both in vitro and in vivo, implying that NaB could represent a novel therapeutic approach for OA.

Grey matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

Brain structural abnormalities in idiopathic restless legs syndrome have long been debated. Voxel-based morphometry is an objective structural magnetic resonance imaging technique to investigate regional grey matter volume or density differences between groups. In the last decade, voxel-based morphometry studies have exhibited inconsistent and conflicting findings regarding the presence and localization of brain grey matter alterations in restless legs syndrome. We therefore conducted a coordinate-based meta-analysis to quantitatively examine whether there were consistent grey matter findings in restless legs syndrome using the latest algorithms, seed-based d mapping with permutation of subject images. We included 12 voxel-based morphometry studies (13 datasets, 375 patients and 385 healthy controls). Our coordinate-based meta-analysis did not identify evidence of consistent grey matter alterations in restless legs syndrome. Grey matter alterations via voxel-based morphometry analysis are not therefore recommended to be used as a reliable surrogate neuroimaging marker for restless legs syndrome. This lack of consistency may be attributed to differences in sample size, genetics, gender distribution and age at onset, clinical heterogeneity (clinical course, anatomical distribution of symptoms, disease severity, disease duration, abnormal sensory profiles and comorbidity), and variations in imaging acquisition, data processing and statistical strategies. Longitudinal studies with multimodal neuroimaging techniques are needed to determine whether structural changes are dynamic and secondary to functional abnormalities.

Cortical thickness in Parkinson's disease: a coordinate-based meta-analysis.

Parkinson's disease (PD) is a common age-related neurodegenerative disease that affects the structural architecture of the cerebral cortex. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis is a popular measure to assess brain structural alterations in the gray matter in PD. However, the results of CTh analysis in PD lack consistency and have not been systematically reviewed. We conducted a comprehensive coordinate-based meta-analysis (CBMA) of 38 CTh studies (57 comparison datasets) in 1,843 patients with PD using the latest seed-based d mapping software. Compared with 1,172 healthy controls, no significantly consistent CTh alterations were found in patients with PD, suggesting CTh as an unreliable neuroimaging marker for PD. The lack of consistent CTh alterations in PD could be ascribed to the heterogeneity in clinical populations, variations in imaging methods, and underpowered small sample sizes. These results highlight the need to control for potential confounding factors to produce robust and reproducible CTh results in PD.

Identification of the molecular mechanisms of Salvia miltiorrhiza relevant to the treatment of osteoarthritis based on network pharmacology.

Traditional Chinese medicine Salvia miltiorrhiza (SM) is a novel application and has shown significant clinical efficacy in treating osteoarthritis (OA). However, the molecular mechanisms of its action have not been systematically evaluated. This study explores the mechanisms of SM in the treatment of osteoarthritis using a network pharmacology approach. In this study, the active ingredients and related targets of SM were obtained following an ADME (absorption, distribution, metabolism, excretion) approach and utilizing the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA-related targets were obtained through GeneCard, PharmGkb, TTD, OMIM, and DRUGBANK databases. The common targets were obtained using the jvenn online tool. The ingredient-target network and the crucial active ingredients were obtained by Cytoscape. The protein-protein interaction (PPI) network and the key targets of SM in the treatment of OA were obtained by the STRING database and Cytoscape. The GO function and KEGG pathway enrichment cluster of the common targets were obtained by Metascape. Molecular docking was obtained by SwissDock to verify the correlation between the crucial active ingredients and key targets. We identified 59 active ingredients including luteolin, tanshinone IIA, dihydrotanshinquinone, and danshenxinkun D with important biological effects in the treatment of OA. We screened 72 common targets of SM-OA, among which IL-6, AKT1, VEGFA, TNF, TP53, FOS, MAPK1, and CASP3 are the key targets. The GO function and KEGG pathway enrichment cluster of the common targets revealed that SM acts on OA mainly through the PI3K-AKT, IL-17, HIF-1, and TNF signaling pathways and that its function is mainly to regulate metabolism, apoptosis, inflammation, and cell proliferation. Moreover, the molecular docking analysis indicated that the crucial ingredients were tightly bound to the key targets. Overall, our study has preliminarily revealed the molecular mechanisms of SM in the treatment of OA through multi-component, multi-target, and multi-channel network pharmacology approaches.

Cortical thickness in Parkinson disease: A coordinate-based meta-analysis.

BACKGROUND: A growing number of studies have used surface-based morphometry (SBM) analyses to investigate gray matter cortical thickness (CTh) abnormalities in Parkinson disease (PD). However, the results across studies are inconsistent and have not been systematically reviewed. A clear picture of CTh alterations in PD remains lacked. Coordinate-based meta-analysis (CBMA) is a powerful tool to quantitatively integrate the results of individual voxel-based neuroimaging studies to identify the functional or structural neural substrates of particular neuropsychiatric disorders. Recently, CBMA has been updated for integrating SBM studies. METHODS: The online databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and SinoMed were comprehensively searched without language limitations from the database inception to February 2, 2020. We will include all SBM studies that compared regional CTh between patients with idiopathic PD and healthy control subjects at the whole-cortex level using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). In addition to the main CBMA, we will conduct several supplementary analyses to test the robustness of the results, such as jackknife analyses, subgroup analyses, heterogeneity analyses, publication bias analyses, and meta-regression analyses. RESULTS: This CBMA will offer the latest evidence of CTh alterations in PD. CONCLUSIONS: Consistent and robust evidence of CTh alterations will feature brain morphometry of PD and may facilitate biomarker development. PROSPERO REGISTRATION NUMBER: CRD42020148775.

Cortical thickness in chronic pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Numerous studies using a variety of non-invasive neuroimaging techniques in vivo have demonstrated that chronic pain (CP) is associated with brain alterations. Cortical thickness (CTh) via surface-based morphometry (SBM) analysis of magnetic resonance imaging data is a valid and sensitive method to investigate the structure of brain gray matter. Many studies have employed SBM to measure CTh difference between patients with CP and pain-free controls and provided important insights into the brain basis of CP. However, the findings from these studies were inconsistent and have not been quantitatively reviewed. METHODS: Three major electronic medical databases: PubMed, Web of Science, and Embase were searched for eligible studies published in English on April 3, 2020. This protocol was prepared based on the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. The Seed-based d Mapping with Permutation of Subject Images software package will be employed to conducted a coordinate-based meta-analysis (CBMA) to identify consistent CTh differences between patients with CP and pain-free controls. Several complementary analyses, including sensitivity analysis, heterogeneity analysis, publication bias, subgroup analysis, and meta-regression analysis, will be further conducted to test the robustness of the results. RESULTS: This CBMA will tell us whether CP with different subtypes shares common CTh alterations and what the pattern of its characterized alterations is. CONCLUSIONS: To the best of our knowledge, this will be the first CBMA of SBM studies that characterizes brain CTh alterations in CP. The CBMA will provide the quantitative evidence of common brain cortical morphometry of CP. The findings will help us to understand the neural basis underlying CP. TRIAL REGISTRATION NUMBER: INPLASY202050069.

Gray matter alterations in restless legs syndrome: A coordinate-based meta-analysis.

BACKGROUND: Voxel-based morphometry (VBM) is an objective structural magnetic resonance imaging (MRI) technique which allows researchers to investigate group-level differences in regional gray matter (GM) volume or density over the whole brain. In the last decade, VBM studies in restless leg syndrome (RLS) have exhibited inconsistent and conflicting findings. METHODS: Studies will be identified through a computerized literature search of the following databases: PubMed, Web of Science, and Embase until October 1, 2018 and updated on March 1, 2020. This protocol will be performed in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P). In addition, we will follow the recent guidelines and recommendations for coordinate-based meta-analysis (CBMA). This CBMA will be performed with the seed-based d mapping with permutation of subject images (SDM-PSI) software. RESULTS: This CBMA will offer the latest evidence of GM alterations in RLS. CONCLUSIONS: To our knowledge, this will be the first CBMA that pooled VBM findings in RLS. This quantitative evidence of GM alterations will characterize brain morphometry of RLS. PROSPERO REGISTRATION NUMBER: CRD42018117014.

Filamin B extensively regulates transcription and alternative splicing, and is associated with apoptosis in HeLa cells.

Post­transcriptional mechanisms are an important approach in the treatment of cancer, and may also be hijacked by tumor cells to help adapt to the local microenvironment. Filamin B (FLNB), an actin­binding protein that provides crucial scaffolds for cell motility and signaling, has also been identified as an RNA­binding protein. Recent studies demonstrated that FLNB might play an important role, not only in skeletal development, but also in regulating tumorigenesis; however, the effects of dysregulated expression of FLNB at the molecular level are not clear. In the present study, RNA­sequencing was performed to analyze changes in overall transcriptional and alternative splicing between the knocked­down FLNB and the control in HeLa cells. Decreased FLNB levels resulted in significantly lower apoptosis compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport and cartilage development. Moreover, FLNB regulated alternative splicing of a large number of genes involved in 'cell death' and the 'apoptotic process'. Some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Reverse transcription­quantitative­PCR identified FLNB­regulated transcription and alternative splicing of genes, such as NLR family apoptosis inhibitory protein, interleukin 23 subunit α, metastasis associated lung adenocarcinoma transcript 1, phosphofurin acidic cluster sorting protein 2, bone morphogenetic protein 7, matrix metallopeptidase 13, collagen type II α 1 chain, fibroblast growth factor receptor 2 and vitamin D receptor. The present study is the first study, to the best of the authors' knowledge, to provide transcriptome­wide analysis of differential gene expression and alternative splicing upon FLNB silencing. The present results suggested that FLNB may play an important regulatory role in cervical cancer cell apoptosis via regulation of transcription and alternative splicing, which provide insight for the current understanding of the mechanisms of FLNB­mediated gene regulation.