The role of lncRNA HCG18 in human diseases.

A substantial number of long noncoding RNAs (lncRNAs) have been identified as potent regulators of human disease. Human leukocyte antigen complex group 18 (HCG18) is a new type of lncRNA that has recently been proven to play an important role in the occurrence and development of various diseases. Studies have found that abnormal expression of HCG18 is closely related to the clinicopathological characteristics of many diseases. More importantly, HCG18 was also found to promote disease progression by affecting a series of cell biological processes. This article mainly discusses the expression characteristics, clinical characteristics, biological effects and related regulatory mechanisms of HCG18 in different human diseases, providing a scientific theoretical basis for its early clinical application.

Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells.

Dysregulation of anti-apoptotic and pro-apoptotic protein isoforms arising from aberrant splicing is a crucial hallmark of cancers and may contribute to therapeutic resistance. Thus, targeting RNA splicing to redirect isoform expression of apoptosis-related genes could lead to promising anti-cancer phenotypes. Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. In this study, through RT-PCR and Western Blot analysis, we found that BCLX pre-mRNA is aberrantly spliced in GBM cells with a favored splicing of anti-apoptotic Bcl-xL. Modulation of BCLX pre-mRNA splicing using splice-switching oligonucleotides (SSOs) efficiently elevated the pro-apoptotic isoform Bcl-xS at the expense of the anti-apoptotic Bcl-xL. Induction of Bcl-xS by SSOs activated apoptosis and autophagy in GBM cells. In addition, we found that ionizing radiation could also modulate the alternative splicing of BCLX. In contrast to heavy (carbon) ion irradiation, low energy X-ray radiation-induced an increased ratio of Bcl-xL/Bcl-xS. Inhibiting Bcl-xL through splicing regulation can significantly enhance the radiation sensitivity of 2D and 3D GBM cells. These results suggested that manipulation of BCLX pre-mRNA alternative splicing by splice-switching oligonucleotides is a novel approach to inhibit glioblastoma tumorigenesis alone or in combination with radiotherapy.

Carrier systems of radiopharmaceuticals and the application in cancer therapy.

Radiopharmaceuticals play a vital role in cancer therapy. The carrier of radiopharmaceuticals can precisely locate and guide radionuclides to the target, where radionuclides kill surrounding tumor cells. Effective application of radiopharmaceuticals depends on the selection of an appropriate carrier. Herein, different types of carriers of radiopharmaceuticals and the characteristics are briefly described. Subsequently, we review radiolabeled monoclonal antibodies (mAbs) and their derivatives, and novel strategies of radiolabeled mAbs and their derivatives in the treatment of lymphoma and colorectal cancer. Furthermore, this review outlines radiolabeled peptides, and novel strategies of radiolabeled peptides in the treatment of neuroendocrine neoplasms, prostate cancer, and gliomas. The emphasis is given to heterodimers, bicyclic peptides, and peptide-modified nanoparticles. Last, the latest developments and applications of radiolabeled nucleic acids and small molecules in cancer therapy are discussed. Thus, this review will contribute to a better understanding of the carrier of radiopharmaceuticals and the application in cancer therapy.

Indisulam exerts anticancer effects via modulation of transcription, translation and alternative splicing on human cervical cancer cells.

Indisulam is a synthetic sulfonamides drug with anticancer activity in various tumors. However, the effect and molecular mechanism of indisulam have still not been studied in human cervical cancer. We treated human cervical cancer cell lines (HeLa and C33A) with indisulam, evaluated its efficacy, and investigated its molecular targets. Indisulam inhibited tumor growth and induced RBM39 degradation in a dose-dependent manner. RNA-seq and proteomics analysis revealed that indisulam disrupted transcriptional regulation pathways related to mRNA splicing and apoptosis. More importantly, indisulam caused mis-splicing of RNA transcripts including p73 isoforms ΔNp73 and TAp73 which have opposite roles in apoptosis regulation. Indisulam increased TAp73 expression and triggered mitochondrial apoptosis independent of p53 status in HeLa cells. In summary, our data suggests that indisulam has therapeutic potential in cervical cancer, representing an attractive strategy in p53-disrupted cancers and should be further investigated.

Ferroptosis: a novel regulated cell death participating in cellular stress response, radiotherapy, and immunotherapy.

BACKGROUND: Ferroptosis is a regulated cell death mode triggered by iron-dependent toxic membrane lipid peroxidation. As a novel cell death modality that is morphologically and mechanistically different from other forms of cell death, such as apoptosis and necrosis, ferroptosis has attracted extensive attention due to its association with various diseases. Evidence on ferroptosis as a potential therapeutic strategy has accumulated with the rapid growth of research on targeting ferroptosis for tumor suppression in recent years. METHODS: We summarize the currently known characteristics and major regulatory mechanisms of ferroptosis and present the role of ferroptosis in cellular stress responses, including ER stress and autophagy. Furthermore, we elucidate the potential applications of ferroptosis in radiotherapy and immunotherapy, which will be beneficial in exploring new strategies for clinical tumor treatment. RESULT AND CONCLUSION: Based on specific biomarkers and precise patient-specific assessment, targeting ferroptosis has great potential to be translated into practical new approaches for clinical cancer therapy, significantly contributing to the prevention, diagnosis, prognosis, and treatment of cancer.

Carbon ions trigger DNA damage response to overcome radioresistance by regulating ß-catenin signaling in quiescent HeLa cells.

Quiescent cancer cells are major impediments to effective radiotherapy (RT) and exhibit limited sensitivity to traditional photon therapy. Herein, the functional role and underlying mechanism of carbon ions in overcoming the radioresistance of quiescent cervical cancer HeLa cells were determined. Briefly, serum withdrawal was used to induce synchronized quiescence in HeLa cells. Quiescent HeLa cells displayed strong radioresistance and DNA repair potential. After irradiation with carbon ions, the DNA damage repair pathway may markedly rely on error-prone nonhomologous end-joining in proliferating cells, whereas the high-precision homologous recombination pathway is more relevant in quiescent cells. This phenomenon could be explained by the ionizing radiation (IR)-induced cell cycle re-entry of quiescent cancer cells. There are three strategies for eradicating quiescent cancer cells using high-linear energy transfer (LET) carbon ions: direct cell death through complex DNA damage; apoptosis via an enhanced mitochondria-mediated intrinsic pathway; forced re-entry of quiescent cancer cells into the cell cycle, thereby improving their susceptibility to IR. Silencing ß-catenin signaling is essential for maintaining the dormant state in quiescent cells. Herein, carbon ions activated the ß-catenin pathway in quiescent cells, and inhibition of this pathway improved the resistance of quiescent HeLa cells to carbon ions by alleviating DNA damage, improving DNA damage repair, maintaining quiescent depth, and inhibiting apoptosis. Collectively, carbon ions conquer the radioresistance of quiescent HeLa cells by activating ß-catenin signaling, which provides a theoretical basis for improved therapeutic effects in patients with middle-advanced-stage cervical cancer with radioresistance.

Aberrant Cyclin D1 splicing in cancer: from molecular mechanism to therapeutic modulation.

Cyclin D1 (CCND1), a crucial mediator of cell cycle progression, possesses many mutation types with different mutation frequencies in human cancers. The G870A mutation is the most common mutation in CCND1, which produces two isoforms: full-length CCND1a and divergent C-terminal CCND1b. The dysregulation of the CCND1 isoforms is associated with multiple human cancers. Exploring the molecular mechanism of CCND1 isoforms has offer new insight for cancer treatment. On this basis, the alterations of CCND1 gene are described, including amplification, overexpression, and mutation, especially the G870A mutation. Subsequently, we review the characteristics of CCND1 isoforms caused by G870A mutation. Additionally, we summarize cis-regulatory elements, trans-acting factors, and the splice mutation involved in splicing regulation of CCND1. Furthermore, we highlight the function of CCND1 isoforms in cell cycle, invasion, and metastasis in cancers. Importantly, the clinical role of CCND1 isoforms is also discussed, particularly concerning prognosis, chemotherapy, and radiotherapy. Last, emphasis is given to the corrective strategies that modulate the cancerous CCND1 isoforms. Thus, it is highlighting significance of aberrant isoforms of CCND1 as targets for cancer therapy.

Influence of cyclin D1 splicing variants expression on breast cancer chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.

Cyclin D1 (CCND1), a mediator of cell cycle control, has a G870A polymorphism which results in the formation of two splicing variants: full-length CCND1 (CCND1a) and C-terminally truncated CCND1 species (CCND1b). However, the role of CCND1a and CCND1b variants in cancer chemoresistance remains unknown. Therefore, this study aimed to explore the molecular mechanism of alternative splicing of CCND1 in breast cancer (BC) chemoresistance. To address the contribution of G870A polymorphism to the production of CCND1 variants in BC chemoresistance, we sequenced the G870A polymorphism and analysed the expressions of CCND1a and CCND1b in MCF-7 and MCF-7/ADM cells. In comparison with MCF-7 cells, MCF-7/ADM cells with the A allele could enhance alternative splicing with the increase of SC-35, upregulate the ratio of CCND1b/a at both mRNA and protein levels, and activate the CDK4/CyclinD1-pRB-E2F1 pathway. Furthermore, CCND1b expression and the downstream signalling pathway were analysed through Western blotting and cell cycle in MCF-7/ADM cells with knockdown of CCND1b. Knockdown of CCND1b downregulated the ratio of CCND1b/a, demoted cell proliferation, decelerated cell cycle progression, inhibited the CDK4/CyclinD1-pRB-E2F1 pathway and thereby decreased the chemoresistance of MCF-7/ADM cells. Finally, CCND1 G870A polymorphism, the alternative splicing of CCDN1 was detected through Sequenom Mass ARRAY platform, Sanger sequencing, semi-quantitative RT-PCR, Western blotting and immunohistochemistry in clinical BC specimens. The increase of the ratio of CCND1b/a caused by G870A polymorphism was involved in BC chemoresistance. Thus, these findings revealed that CCND1b/a ratio caused by the polymorphism is involved in BC chemoresistance via CDK4/CyclinD1-pRB-E2F1 pathway.

A novel PTEN mutant caused by polymorphism in cis-regulatory elements is involved in chemosensitivity in breast cancer.

Phosphatase and tensin homolog (PTEN) is one of the most important tumor suppressor genes. Although studies have shown the association between cancer and genetic polymorphisms of PTEN, the underlying molecular mechanisms of breast cancer (BC) chemosensitivity that results from PTEN polymorphism is still unclear. This study aims to investigate potential links between PTEN polymorphisms in cis-regulatory elements and BC chemosensitivity in the Chinese population. A total of 172 BC patients who received neoadjuvant chemotherapy were included in the study, including 104 chemosensitive cases and 68 chemoresistant cases. The results showed a significant association between the rs786204926 polymorphism and BC chemosensitivity. Logistic multivariate regression analysis showed that age, lymph node metastasis, and the rs786204926 genotype were risk factors for BC chemoresistance. The G allele of rs786204926 is more prone to increasing the risk of chemosensitivity in BC. Additionally, analysis using Alamut Visual showed a preference of the G allele of rs786204926 to produce a novel PTEN mutant with an insertion of 18 bases from intron 4. While the transcriptional level of PTEN remained similar in chemosensitivity and chemoresistant samples, its protein level changed significantly. Interestingly, there were significant differences in both transcription and protein levels of the novel PTEN mutant between the two groups. Furthermore, we found that the mutant was more susceptible to dephosphorylation compared with wildtype PTEN, leading to chemosensitivity through the PI3K-AKT signaling pathway. These findings indicate that novel PTEN mutants caused by polymorphisms in cis-regulatory elements may be involved in BC chemosensitivity.

Double-sided plasmonic metasurface for simultaneous biomolecular separation and SERS detection.

Porous membrane-based nanofiltration separation of small biomolecules is a widely used biotechnology for which size-based selectivity is a critical parameter of technological relevance. Efficient determination of size selectivity calls for an advanced detection method capable of performing sensitive, rapid, and on-membrane examination. Surface-enhanced Raman spectroscopy (SERS) is such a detection method that has been widely recognized as an ultrasensitive technique for trace-level detection with sensitivity down to the single-molecule level. In this work, we for the first time develop a double-sided hierarchical porous membrane-like plasmonic metasurface to realize high-selectivity bimolecular separation and simultaneous ultrasensitive SERS detection. This highly flexible device, consisting of subwavelength nanocone pairs surrounded by randomly orientated sub-5 nm nanogrooves, was prepared by combining customized "top-down" fabrication of conical nanopores in an ion-track registered polycarbonate membrane and self-assembly of nanogrooves on the membrane surface through physical vapor deposition. The unique tip-to-tip oriented conical nanopores in the device enables excellent size-based molecular selectivity; the hierarchical groove-pore structure supports a peculiar cascaded electromagnetic near-field enhancement mechanism, endowing the device with SERS-based molecular detection of ultrahigh sensitivity, uniformity, repeatability, and polarization independence. With such dual structural merits and performance enhancement, we demonstrate effective nanofiltration separation of small-sized adenine from big-sized ss-DNA and synergistic SERS determination of their species. We experimentally demonstrate an ultrasensitive detection of 4-mercaptopyridine down to 10 pM. Together with its unparalleled mechanical flexibility, this double-side-responsive plasmonic metasurface membrane can find great potential in real-world molecular filtration and detection under extremely complex working conditions.

Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.

TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed "gain-of-function". Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.

Overexpression of splicing factor poly(rC)-binding protein 1 elicits cycle arrest, apoptosis induction, and p73 splicing in human cervical carcinoma cells.

PURPOSE: Splicing factor poly(rC)-binding protein 1 (PCBP1) is a novel tumor suppressor that is downregulated in several cancers thereby regulating tumor formation and metastasis. However, the involvement of PCBP1 in apoptosis of cancer cells and the molecular mechanism remains elusive. On this basis, we sought to investigate the role of splicing factor PCBP1 in the apoptosis in human cervical cancer cells. METHODS: To investigate PCBP1 functions in vitro, we overexpressed PCBP1 in human cervical cancer cells. A series of cytological function assays were employed to study to the role of PCBP1 in cell proliferation, cell cycle arrest and apoptosis. RESULTS: Overexpression of PCBP1 was found to greatly repress proliferation of HeLa cells in a time-dependent manner. It also induced a significant increase in G2/M phase arrest and apoptosis. Furthermore, overexpressed PCBP1 favored the production of long isoforms of p73, thereby inducing upregulated ratio of Bax/Bcl-2, the release of cytochrome c and the expression of caspase-3. CONCLUSION: Our results revealed that PCBP1 played a vital role in p73 splicing, cycle arrest and apoptosis induction in human cervical carcinoma cells. Targeting PCBP1 may be a potential therapeutic strategy for cervical cancer therapy.

A positive feedback circuit comprising p21 and HIF-1α aggravates hypoxia-induced radioresistance of glioblastoma by promoting Glut1/LDHA-mediated glycolysis.

The radioresistance induced by hypoxia is the major obstacle in the successful treatment of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, through which mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. In this study, we discovered a novel function of p21, which participated in the regulation of metabolic pathways under hypoxia. We found that p21 was upregulated in glioblastoma (GBM) cells under hypoxic conditions, which enhanced the radioresistance of GBM cells. In principle, HIF-1α is bound directly to the hypoxia response elements (HREs) of the p21 promoter to enhance its transcription activity, in turn, p21 also promoted the transcription of HIF-1α at the mRNA level and maintained HIF-1α function under oxygen deficiency. The positive correlation between p21 and HIF-1α augmented Glut1/LDHA-mediated glycolysis and aggravated the radioresistance of GBM cells. Thus, our results constructed a positive feedback circuit comprising p21/HIF-1α that might play a key role in enhancing the radioresistance of GBM under hypoxia.

RNA-binding protein 39: a promising therapeutic target for cancer.

RNA-binding motif protein 39 (RBM39), as a key factor in tumor-targeted mRNA and protein expression, not only plays a vital role in tumorigenesis, but also has broad development prospects in clinical treatment and drug research. Moreover, since RBM39 was identified as a target of sulfonamides, it has played a key role in the emerging field of molecule drug development. Hence, it is of great significance to study the interaction between RBM39 and tumors and the clinical application of drug-targeted therapy. In this paper, we describe the possible multi-level regulation of RBM39, including gene transcription, protein translation, and alternative splicing. Importantly, the molecular function of RBM39 as an important splicing factor in most common tumors is systematically outlined. Furthermore, we briefly introduce RBM39's tumor-targeted drug research and its clinical application, hoping to give reference significance for the molecular mechanism of RBM39 in tumors, and provide reliable ideas for in-depth research for future therapeutic strategies.

Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.

Bcl-x pre-mRNA splicing serves as a typical example to study the impact of alternative splicing in the modulation of cell death. Dysregulation of Bcl-x apoptotic isoforms caused by precarious equilibrium splicing is implicated in genesis and development of multiple human diseases, especially cancers. Exploring the mechanism of Bcl-x splicing and regulation has provided insight into the development of drugs that could contribute to sensitivity of cancer cells to death. On this basis, we review the multiple splicing patterns and structural characteristics of Bcl-x. Additionally, we outline the cis-regulatory elements, trans-acting factors as well as epigenetic modifications involved in the splicing regulation of Bcl-x. Furthermore, this review highlights aberrant splicing of Bcl-x involved in apoptosis evade, autophagy, metastasis, and therapy resistance of various cancer cells. Last, emphasis is given to the clinical role of targeting Bcl-x splicing correction in human cancer based on the splice-switching oligonucleotides, small molecular modulators and BH3 mimetics. Thus, it is highlighting significance of aberrant splicing isoforms of Bcl-x as targets for cancer therapy.

Crosstalk of the Caspase Family and Mammalian Target of Rapamycin Signaling.

Cell can integrate the caspase family and mammalian target of rapamycin (mTOR) signaling in response to cellular stress triggered by environment. It is necessary here to elucidate the direct response and interaction mechanism between the two signaling pathways in regulating cell survival and determining cell fate under cellular stress. Members of the caspase family are crucial regulators of inflammation, endoplasmic reticulum stress response and apoptosis. mTOR signaling is known to mediate cell growth, nutrition and metabolism. For instance, over-nutrition can cause the hyperactivation of mTOR signaling, which is associated with diabetes. Nutrition deprivation can inhibit mTOR signaling via SH3 domain-binding protein 4. It is striking that Ras GTPase-activating protein 1 is found to mediate cell survival in a caspase-dependent manner against increasing cellular stress, which describes a new model of apoptosis. The components of mTOR signaling-raptor can be cleaved by caspases to control cell growth. In addition, mTOR is identified to coordinate the defense process of the immune system by suppressing the vitality of caspase-1 or regulating other interferon regulatory factors. The present review discusses the roles of the caspase family or mTOR pathway against cellular stress and generalizes their interplay mechanism in cell fate determination.

A SNP involved in alternative splicing of ABCB1 is associated with clopidogrel resistance in coronary heart disease in Chinese population.

Although many scientists are studying the association between genetic polymorphism of ABCB1 and CR in patients, the molecular mechanism has not been further studied in patients with CHD. This study investigated the relationship between SNP of the ABCB1 gene in patients with CHD and CR, and whether the polymorphism of the ABCB1 gene affects the AS of the gene. 741 patients were enrolled in the study, 316 CR cases and 425 NCR cases. The correlation between CR risk and clinical-pathological characteristics were studied. Additionally, the five SNPs were analysed by PCR and Mass Array genotyping methods. Furthermore, silicon analysis was used to predict whether the polymorphism affects the process of AS. Results showed that there was a significant correlation between rs1045642 polymorphism and CR in genotyping and allele analysis. The rs1045642 polymorphism of the ABCB1 gene of CHD patients carrying the A allele are more likely to develop CR. Silicon analysis showed that rs1045642 generated a new ESE sequence which might affect AS of ABCB1 gene. We hypothesize that the mechanism of CR might be caused by a change in the AS caused by the polymorphism of the gene. Thus, this work provides guidance for the clinical use of clopidogrel.

Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction.

AIMS: Mitochondrial dysfunction is receiving considerable attention due to irreplaceable biological function of mitochondria. Ionizing radiation and tigecycline (TIG) alone can cause mitochondrial dysfunction, playing important role in tumor therapy. However, prior studies fail to investigate combined mechanism of carbon ion irradiation (IR) and TIG on tumor proliferation inhibition. The study aimed to explore the combined effects of both on autophagy and apoptosis. MATERIALS AND METHODS: NSCLC cells A549 and H1299 were treated with carbon ion, TIG, or both. Cell survival rate, autophagy, apoptosis, expression of mitochondrial signaling proteins were determined by clone formation assay, immunofluorescence of LC3B, flow cytometry and western blotting, respectively; ATP content, mitochondrial membrane potential (MMP) and Ca2+ level in mitochondria were used to assessed mitochondrial function. KEY FINDINGS: Results showed IR combined TIG inhibited cells proliferation by increasing apoptosis in both cells and enhancing autophagy in H1299 cells. Additionally, combination treatment induced the most severe mitochondrial dysfunction by sharply reducing ATP, MMP and increasing Ca2+ level of mitochondria. Up-regulation and down-regulation of mitochondrial translation proteins (EF-Tu, GFM1 and MRPS12) expression affected apoptosis and autophagy, while the level of p-mTOR was consistent with their expression in both cell types. In A549 cells, p-AMPK level decreased while p-Akt and p-mTOR increased after combination treatment. SIGNIFICANCE: Overall, our results showed that p-Akt and p-AMPK antagonistically targeted p-mTOR to regulate mitochondrial translation proteins to affect autophagy and apoptosis. Furthermore, this study suggests that combination of carbon ion and TIG is a potential therapeutic option against tumors.

Multilevel regulation and molecular mechanism of poly (rC)-binding protein 1 in cancer.

Poly (rC)-binding protein 1 (PCBP1), an RNA- or DNA-binding protein with a relative molecular weight of 38 kDa, which is characterized by downregulation in many cancer types. Numerous cases have indicated that PCBP1 could be considered as a tumor suppressor to inhibit tumorigenesis, development, and metastasis. In the current review, we described the multilevel regulatory roles of PCBP1, including gene transcription, alternative splicing, and translation of many cancer-related genes. Additionally, we also provided a brief overview about the inhibitory effect of PCBP1 on most common tumors. More importantly, we summarized the current research status about PCBP1 in hypoxic microenvironment, autophagy, apoptosis, and chemotherapy of cancer cells, aiming to clarify the molecular mechanisms of PCBP1 in cancer. Taken together, in-depth study of PCBP1 in cancer may provide new ideas for cancer therapy.

MicroRNA­16­5p regulates cell survival, cell cycle and apoptosis by targeting AKT3 in prostate cancer cells.

Prostate cancer (PCa) is a malignancy with the highest morbidity rate in 105 countries worldwide and was a major cause of cancer­associated death in men in 2018. Accumulating evidence suggests that microRNAs (miRNAs/miRs) have important functions in the carcinogenesis of PCa, and may provide novel treatment targets. Previous studies have indicated that miR­16­5p is associated with PCa. However, the relevance and importance of miR­16­5p in PCa carcinogenesis are still not completely understood. In the current study, we aimed to investigate the role and mechanism of miR­16­5p in PCa carcinogenesis. The results showed that miR­16­5p was markedly downregulated in PCa cells, and MTS assay, colony formation, flow cytometric analyses demonstrated that miR­16­5p inhibited PCa cell survival, regulated cell cycle distribution and induced apoptosis. Moreover, luciferase reporter assay and western blot analysis showed that miR­16­5p directly targets AKT3 (AKT serine/threonine kinase 3), which is associated with PCa carcinogenesis, and the effects of the downregulation of AKT3 were similar to the effects of upregulation of miR­16­5p in PC­3 cells. In conclusion, our data clarify that miR­16­5p has anticancer functions in PCa cells, and our findings provide experimental evidence to highlight the potential value of miR­targeting treatment strategies for PCa.