Serum exosomes are emerging as key liquid biopsy biomarkers for the early diagnosis of cancer. However, the proportion and distribution of small RNA (sRNA) species from serum exosomes of hepatocellular carcinoma (HCC) patients remain unclear. Effective and reliable biomarkers for HCC diagnosis should be explored.In this study, we aimed to use sRNA sequencing to profile the sRNAs of serum exosomes in HCC and non-tumor donors. The serum exosomes of 124 HCC patients and 46 non-tumor donors were enrolled for detecting the values of the potential biomarkers for the diagnosis of HCC.We found that miRNAs accounted for the maximal percentage of all types of sRNAs both in the serum exosomes of HCC patients and non-tumor donors. This indicated that the serum-exosome-derived microRNAs (miRNAs) were the most valuable as potential biomarkers in HCC diagnosis. Then, miRNAs were set as research candidates. In our Chinese cohorts, three serum-exosome-derived miRNAs (miR-122-5p, let-7d-5p, and miR-425-5p) could be promising biomarkers for distinguishing HCC patients from non-tumor donors. In addition, they were preferred for the early diagnosis of HCC. We also presented the base distribution of some novel serum-exosome-derived miRNAs and described the potential values as biomarkers.The results suggested that the serum-exosome-derived miRNAs were the most crucial sRNA species and they highlighted the potential of serum-exosome-derived miRNAs as promising biomarkers for HCC diagnosis.
: Fibroadenomas are the most common breast masses in adolescent women. Giant fibroadenomas are an uncommon disease during pregnancy and lactation. Significant enlargement might result in breast asymmetry and deformity. We present a rare case of giant fibroadenoma during pregnancy and lactation with significant breast asymmetry. Excision with round block technique leaves a discrete scar and a cosmetic contour.
MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro.We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins.Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b.Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.
Background: MicroRNAs (miRNAs) play an essential role in the initiation, progression and metastasis of breast cancer. It has been confirmed that miR-30b is involved in various cancers. However, the specific involvement of miR-30b on breast cancer metastasis remains unknown. In the current study, we aimed to investigate the role of miR-30b in the progression and metastasis of breast cancer in vitro.
Methods: We up-regulated the expression of miR-30b in breast cancer cell lines SKBR3 and MDA-MB-231 by transfecting pCMV-miR-30b vector. CCK8, colony formation, Transwell, and flow cytometry assays were used to examine cell proliferation, migration, invasion and apoptosis, respectively. A dual-luciferase reporter assay was performed to identify the relationship between miR-30b and the target gene. Western blot assay was used to detect related proteins.
Results: Our data showed that the overexpression of miR-30b significantly inhibited proliferation, migration and invasion abilities in SKBR3 and MDA-MB-231 cells. Meanwhile, overexpression of miR-30b induced cell apoptosis for both SKBR3 and MDA-MB-231 cells by regulating the expression of apoptosis-related proteins (Bcl-2, Bax, active Caspase-3, and Caspase-9). Moreover, miR-30b inhibited the activation of the PI3K/Akt signaling pathway by decreasing the phosphorylation levels of Akt and mTOR. Furthermore, we determined that miR-30b could down-regulate the expression of Derlin-1 in a post-transcriptional manner by employing the dual-luciferase reporter and western blot assays. Further analysis demonstrated that depletion of Derlin-1 inhibited Akt phosphorylation, and Derlin-1 could restore the effect of miR-30b on Akt. In addition, the CCK8 assay showed that Derlin-1 could partly reverse the inhibition of cell proliferation of SKBR3 and MDA-MB-231 cells mediated by miR-30b.
Conclusions: Our data demonstrated that miR-30b suppresses the progression and metastasis of breast cancer via inhibition of the PI3K/Akt signaling pathway by targeting Derlin-1 in vitro. This suggests that miR-30b might be a novel potent target for breast cancer therapy.
Abstract Mitophagy, a form of selective autophagy that removes damaged or dysfunctional mitochondria, plays a crucial role in maintaining mitochondrial and cellular homeostasis. Recent findings suggest that defective mitophagy is closely associated with various diseases, including breast cancer. Moreover, a better understanding of the multifaceted roles of mitophagy in breast cancer progression is crucial for the treatment of this disease. Here, we will summarize the molecular mechanisms of mitophagy process. In addition, we highlight the expression patterns and roles of mitophagy-related signaling molecules in breast cancer progression and the potential implications of mitophagy for the development of breast cancer, aiming to provide better therapeutic strategies for breast cancer treatment.
tRNA-derived fragments (tRFs), a novel class of small non-coding RNAs cleaved from transfer RNAs, have been implicated in tumor regulation. In this study, the role of a specific tRF, HCETSR is investigated, which is significantly downregulated in hepatocellular carcinoma (HCC) and correlates with advanced tumor burden and higher HCC mortality. Functional analyses revealed that HCETSR inhibits HCC malignancy and serves as an independent predictor of poor prognosis. Mechanistically, a novel SPTBN1/catenin complex axis regulated by HCETSR is identified. HCETSR binds to a critical domain of SPTBN1, disrupting its interaction with the catenin complex (comprising β-catenin, α-catenin, and P120-catenin), and facilitates the transfer of the catenin complex from the cell membrane to the nucleus. Specifically, HCETSR decreases the proteasomal degradation of β-catenin and inhibits the synthesis of nascent β-catenin. Furthermore, HCETSR suppresses the transcriptional activity of LEF1 through P120-catenin rather than α-catenin, thereby reducing β-catenin's influence on LEF1 activity. It is demonstrated that HCETSR is spliced from tRNA-Glu/TTC. The biogenesis of HCETSR and tRNA-Glu/TTC is regulated by the spliceosome and Dicer1. In conclusion, These findings suggest that HCETSR, derived from tRNA-Glu/TTC, inhibits HCC malignancy via modulation of the SPTBN1/catenin axis and may represent a promising prognostic marker and therapeutic strategy for HCC.
Objective. To study the effect of Rhizopus nigricans exopolysaccharide EPS1-1 on the proliferation, apoptosis, and migration of breast cancer MCF-7 cells. Methods. Human breast cancer MCF-7 cells were cultured in vitro and treated with different concentrations of EPS1-1. The effect of EPS1-1 on cell proliferation was tested by the CCK-8 experiment, and the effect of EPS1-1 on cell apoptosis was determined by flow cytometry. And the scratch test was used to detect the impact of EPS1-1 on cell migration. Western blot then was used to measure the expression changes of related proteins in the Akt signaling pathway. Results. Compared with the control group, treatment with EPS1-1 significantly reduced the proliferation, migration, and invasion ability of MCF-7 cells and promoted the apoptosis of MCF-7 cells in a dose-dependent manner. In terms of the underlying mechanism, EPS1-1 can significantly inhibit the phosphorylation of Akt at threonine 308 and serine 473 and cause the expression changes of downstream proliferation-related genes CCND1 and p21, apoptosis-related genes Bcl-2 and Bax, and migration-related genes Vimentin and E-cadherin in terms of their protein levels. Conclusion. EPS1-1 can inhibit the proliferation, migration, and invasion of breast cancer MCF-7 cells and promote the apoptosis of MCF-7 cells by inhibiting the activation of the Akt signaling pathway. Therefore, EPS1-1 can be used as a potential new drug or adjuvant drug for the treatment of breast cancer.
Objective To investigate the protective effects of bone marrow mesenchymal stem cells transplantation (MSCT) and mobilization on severe acute pancreatitis (SAP) with acute renal injury.Methods A total of 240 SD rats were randomly divided into sham operation group ( n =48 ),model control group ( n =48 ),MSCT group ( n =48),bone marrow mesenchymal stem cells mobilization (MSCM) group ( n =48) and MSCT +MSCM group ( n =48 ) according to the random number table.Rat models of SAP were made by peritoneal injection of L-arginine.Rats in the MSCT group were injected with 1.2 ml of bone marrow mesenchymai stem cells via femoral vein at 6 hours after SAP model establishment; rats in the MSCM group were subcutaneously injected with 40 μg/kg of granulocyte-colony stimulating factor (G-CSF) at 3 days before SAP model establishment; rats in the MSCT + MSCM group were injected with 1.2 ml of MSC and 40 μg/kg of G-CSF simultaneously; rats in the sham operation group were injected with equal volume of normal saline.According to different time points after operation,rats in each group were subdivided into 12 h,24 h,48 h and 72 h groups (n =12).At each time points after operation,the mortality rate,pathological changes of renal tissue,expression of Bax protein,Bcl-2 protein and apoptosis indexes of renal tubular epithelium cells were observed.The contents of tumor necrotic factor-α (TNF-α),interleukin-6 (IL-6),blood urea nitrogen (BUN),creatinine (Cr),lactate dehydrogenase (LDH) and C-reactive protein (CRP) were determined.All data were analyzed by using SNK-q test,Fisher exact probability and analysis of variance.Results All rats in the sham operation group were survived.The numbers of rats in the model control group survived at postoperative 48 hours and 72 hours were 11 and 8,respectively.No rat died at postoperative 48 hours in the MSCT group,MSCM group and MSCT + MSCM group.The numbers of rats survived at postoperative 72 hours in the MSCT group,MSCM group and MSCT + MSCM group were 11,10 and 11,which were not significantly different from the number of survived rats in the model control group (P ＞0.05).The pathological injuries of renal tissues were relieved in the MSCT group,MSCM group and MSCT + MSCM group when compared with model control group.The expression of Bax protein,Bc1-2 protein,renal tubular epithelium cell apoptosis indexes at 12-72 hours were 12.80 + 1.78-20.30 + 2.40,4.34 + 1.20-3.03 ± 1.06,12.65％ ±2.31％-35.10％ ± 5.54％ in the model control group,9.68 ± 2.11-17.01 ± 2.54,5.57 ± 1.35-4.13 + 1.05,6.20％ ± 1.53％- 17.50％ ± 2.80％ in the MSCT group,10.05 ± 2.17-16.81 ± 2.55,5.49 ± 1.48-4.19 ±1.05,6.41％± 1.64％-17.14％±2.27％ in the MSCM group,8.33 ±2.06-14.03 ±2.27,6.60 ±2.11-5.63 ±1.52,5.80％ ± 1.52％-12.30％ ±2.43％ in the MSCT + MSCT group.There were significant differences in the expressions of Bax protein at 24 and 72 hours,Bcl-2 protein at 48 and 72 hours,renal tubular epithelium cell apoptosis index at 24,48 and 72 hours between the MSCT group,MSCM group and MSCT + MSCM group ( P ＜0.05 ),but no significant difference was found between the MSCT group and the MSCM group ( P ＞ 0.05 ).The contents of TNF-α,IL-6,BUN,Cr,LDH,CRP in the MSCT group,MSCM group and MSCT + MSCM group were decreased when compared with those in the model control group,and a significant decrease of the 6 factors was observed in the MSCT + MSCM group.There were significant difference in the content of TNF-α at 72 hours,IL-6,BUN and Cr at 48 and 72 hours,LDH at 24,48 and 72 hours and CRP at 72 hours between the MSCT group,MSCM group and MSCT + MSCM group (P ＜0.05),while no significant difference was observed between the MSCT group and the MSCM group (P ＞ 0.05).Conclusion MSCT and MSCM can significantly protect acute renal injury in the progress of SAP,the probable mechanisms are pathological regeneration,anti-inflammatory effect and apoptosis inhibition of mesenchymal stem cells.
Key words:
Severe acute pancreatitis; Mesenchymal stem cells; Transplantation; Kidney; Cellapoptosis
Background: Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC. Methods: We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study. Results: We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden. Conclusion: piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis. Keywords: biomarker, exosome, sRNA-seq, HCC, piRNA
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