miR-141 Regulates Proliferation and Apoptosis of Renal Clear Cell Carcinoma by Targeting Phosphatase and Tensin Homolog (PTEN)

2020 ◽  
Vol 10 (5) ◽  
pp. 676-681
Author(s):  
Jianjun Zhao ◽  
Chao Tan ◽  
Haibin Chen ◽  
Xiaolong Cheng ◽  
Limei Hui
Keyword(s):  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Tumor Tissues ◽  
Pten Mrna ◽  
Relationship Of

Objective: PTEN inhibits the activity of PI3K/AKT pathway. Abnormal miR-141 expression is associated with kidney cancer. Bioinformatics analysis revealed a relationship of miR-141 with PTEN. This study assessed miR-141's role in renal cancer cells. Methods: The dual luciferase reporter gene assay validated the relationship of miR-141 with PTEN. The tumor tissues and adjacent tissues of patients with renal cell carcinoma were collected to measure miR-141 and PTEN level. A498 cells were divided into miR-NC group and miR-141 inhibitor group followed by analysis of the expressions of miR-141, PTEN and p-AKT, cell apoptosis and proliferation by flow cytometry. Results : There is a relationship of miR-141 with PTEN. Compared with those in adjacent tissues, miR-141 was upregulated and PTEN mRNA was downregulated in tumor tissues. There was a negative correlation between miR-141 and PTEN mRNA (r = – 0 646,P < 0 001). Compared with that in HK-2 cells, miR-141 expression was increased in RCC4 and A498 cells, with decreased PTEN expression. Transfection of miR-141 inhibitor significantly up-regulated PTEN in A498 cells, reduced PI3K/AKT signaling activity, decreased cell proliferation and colony formation, as well as promoted cell apoptosis. Conclusion: miR-141 participates in reducing PTEN expression and promoting the pathogenesis of renal cancer. Inhibiting miR-141 expression up-regulates PTEN, inhibits PI3K/AKT signaling, and attenuates proliferation and promotes apoptosis of renal cancer cells.

miR-203 Regulates Proliferation and Apoptosis of Colorectal Cancer Cells Through Targeting DJ-1

2020 ◽  
Vol 10 (3) ◽  
pp. 365-370
Author(s):  
Qiupeng Du ◽  
Na Du ◽  
Chenchen Zhu ◽  
Qingqing Shang ◽  
Haiyan Mao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Pten Expression ◽  
Proliferation And Apoptosis ◽  
Colorectal Cancer Cells ◽  
Colorectal Cell ◽  
Sw480 Cells

Objective: To assess whether miR-203 regulates DJ-1 expression, affects colorectal cancer cells through PTEN-PI3K/AKT signaling. Methods: Colorectal cancer (CRC) tissues and adjacent tissues were collected followed by analysis of the level of miR-203, DJ-1 and PTEN. miR-203 and DJ-1 level was measured in HCT116, SW480 and normal colorectal cell NCM460. miR-203 mimic or miR-NC was transfected into HCT116 or SW480 cells followed by measuring the level of miR-203, DJ-1, PTEN, p-AKT as well as cell apoptosis and proliferation. Results: Compared with tumor adjacent tissues, tumor tissues showed significantly lower level of miR-203 and PTEN, and higher level of DJ-1. There is a targeted relationship between miR-203 and DJ-1. Compared with NCM460 cell, HCT116 and SW480 cells displayed significantly lower miR-203 level and higher DJ-1 expression. miR-203 mimic significantly reduced DJ-1 and p-AKT level, increased PTEN expression, cell apoptosis and inhibited cell proliferation. Conclusion: Lower miR-203 and higher DJ-1 level is found in CRC patients. Upregulation of miR-203 inhibits DJ-1 expression, increases PTEN expression, impairs PI3K/AKT signaling, inhibits CRC cell proliferation and promotes apoptosis.

scholarly journals Silencing of MEG3 attenuated the role of lipopolysaccharides by modulating the miR-93-5p/PTEN pathway in Leydig cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xu Zhou ◽  
Jingliang He ◽  
Jinbo Chen ◽  
Yu Cui ◽  
Zhenyu Ou ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Leydig Cells ◽  
Treatment Strategies ◽  
Pten Expression ◽  
Luciferase Reporter ◽  
Western Blots ◽  
New Treatment ◽  
Lps Treatment

Abstract Background Leydig cells reflect the activation of inflammation, decrease of androgen production, inhibition of cell growth and promotion of cell apoptosis under orchitis. Maternally expressed gene 3 (MEG3) exerts a crucial role in various human diseases, but under orchitis, the role and underlying molecular mechanism of MEG3 in Leydig cells remain unclear. Methods Lipofectamine 2000 was used for the cell transfections. qPCR and western blots assay were applied to assess the gene expression. ELISA assay was used to measure the TNFα, IL6 and testosterone secretion. CCK8 and EdU assay was employ to test the cell viability and proliferation respectively. Luciferase reporter and RIP assay were introduced to detect the binding of miR-93-5p with MEG3 and PTEN. Results Lipopolysaccharides (LPS) induced TNFα and IL6 secretion, lowered testosterone production, inhibited cell viability and proliferation, and induced cell apoptosis in Leydig cells. MEG3 was upregulated in Leydig cells treated with LPS and that knockdown of MEG3 inhibited the role of LPS in Leydig cells. MEG3 absorbed miR-93-5p and that suppression of miR-93-5p restored the role of silenced MEG3 in Leydig cells under LPS treatment. miR-93-5p inhibited PTEN expression and that over-expressed PTEN alleviated the effect of miR-93-5p in Leydig cells treated with LPS. LPS activated the MEG3/miR-93-5p/PTEN signalling pathway in Leydig cells. Conclusions This study revealed that MEG3 serves as a molecular sponge to absorb miR-93-5p, thus leading to elevation of PTEN expression in Leydig cells under LPS treatment, offering a theoretical basis on which to establish potential new treatment strategies for orchitis.

Effect of host immunity on metastatic potential in renal cell carcinoma: the assessment of optimal in vivo models to study metastatic behavior of renal cancer cells

Tumor Biology ◽  
2012 ◽  
Vol 33 (2) ◽  
pp. 551-559 ◽  
Author(s):  
Minoru Kobayashi ◽  
Tatsuo Morita ◽  
Nicole A. L. Chun ◽  
Aya Matsui ◽  
Masafumi Takahashi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Metastatic Potential ◽  
Host Immunity ◽  
In Vivo Models ◽  
Metastatic Behavior

scholarly journals Tumor-derived extracellular vesicles inhibit HGF/c-Met and EGF/EGFR pathways to accelerate the radiosensitivity of nasopharyngeal carcinoma cells via microRNA-142-5p delivery

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Changyu Zhu ◽  
Xiaolei Jiang ◽  
Hua Xiao ◽  
Jianmei Guan
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Extracellular Vesicles ◽  
Nude Mice ◽  
Peripheral Blood ◽  
Cell Apoptosis ◽  
Expression Patterns ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Relationship Of ◽  
Dual Luciferase Reporter Assay

AbstractRadioresistance prevails as one of the largest obstacles in the clinical treatment of nasopharyngeal carcinoma (NPC). Meanwhile, tumor-derived extracellular vesicles (TEVs) possess the ability to manipulate radioresistance in NPC. However, its mechanism remains to be further explored. Therefore, the current study set out to explore the mechanism of microRNA (miR)-142-5p delivered by TEVs in regard to the radiosensitivity of NPC. Firstly, peripheral blood samples were collected from patients with radioresistance and radiosensitivity, followed by RT-qPCR detection of miR-142-5p expression. A dual-luciferase reporter assay was carried out to elucidate the targeting relationship of miR-142-5p with HGF and EGF. In addition, radiotherapy-resistant NPC cell models were established by screening NPC cells with gradient increasing radiation exposure, and co-incubated with EVs isolated from miR-142-5p mimic-transfected NPC cells, followed by overexpression of HGF and EGF. Moreover, cell viability was detected by means of MTS, cell proliferation with a colony formation assay, cell apoptosis with flow cytometry, and expression patterns of related genes with the help of Western blot analysis. NPC xenotransplantation models in nude mice were also established by subcutaneous injection of 5-8FR cells to determine apoptosis, tumorigenicity, and radiosensitivity in nude mice. It was found that miR-142-5p was poorly expressed in peripheral blood from NPC patients with radioresistance. Mechanistic experimentation illustrated that miR-142-5p inversely targeted HGF and EGF to inactivate the HGF/c-Met and EGF/EGFR pathways, respectively. NPC cell apoptosis was observed to be augmented, while their radioresistance and proliferation were restricted by EVs-miR-142-5p or HGF silencing, or EGF silencing. Furthermore, EVs-miR-142-5p inhibited growth and radioresistance and accelerated the apoptosis of radiotherapy-resistant NPC cells in nude mice by inhibiting the HGF/c-Met and EGF/EGFR pathways. Collectively, our findings indicated that TEVs might inhibit the HGF/c-Met and EGF/EGFR pathways by delivering miR-142-5p into radiotherapy-resistant NPC cells to enhance radiosensitivity in NPC.

scholarly journals Circular RNA circMTO1 Suppresses RCC Cancer Cell Progression via miR9/LMX1A Axis

2020 ◽  
Vol 19 ◽  
pp. 153303382091428
Author(s):  
Kecheng Li ◽  
Cheng-Liang Wan ◽  
Yan Guo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
Target Genes ◽  
Cell Function ◽  
Circular Rnas ◽  
Promoting Effect

Renal cell carcinoma is one of the most common kidney cancer, which accounts almost 90% of the adult renal malignancies worldwide. In recent years, a new class of endogenous noncoding RNAs, circular RNAs, exert important roles in cell function and certain types of pathological responses, especially in cancers, generally by acting as a microRNA sponge. Circular RNAs could act as sponge to regulate the microRNA and the target genes. However, the knowledge about circular RNAs in renal cell carcinoma remains unclear so far. In the research, we selected a highly expressed novel circular RNAs named circMTO1 in renal cell carcinomas. We investigated the roles of circMTO1 and found that circMTO1 overexpression could suppress cell proliferation and metastases in both A497 and 786-O renal cancer cells, while silencing of circMTO1 could promote the progression in SN12C and OS-RC-2 renal cancer cells. The study showed that circMTO1 acted as miR9 and miR223 sponge and inhibited their levels. Furthermore, silencing of circMTO1 in renal cell carcinoma could downregulate LMX1A, the target of miR-9, resulting in the promotion of renal cell carcinoma cell proliferation and invasion. In addition, LMX1A expression suppression induced by transfection of miR9 mimics confirmed that miR9 exerted its function in renal cell carcinoma by regulating LMX1A expression. What’s more, miR9 inhibitor and LMX1A overexpression could block the tumor-promoting effect of circMTO1 silencing. In conclusion, circMTO1 suppresses renal cell carcinoma progression by circMTO1/miR9/ LMX1A, indicating that circMTO1 may be a potential target in renal cell carcinoma therapy.

miR-9-5p Increases Sensitivity to Cisplatin in Thyroid Cancer Cells by Down-Regulating BRAF Expression

2019 ◽  
Vol 9 (6) ◽  
pp. 751-759
Author(s):  
Wanzhi Chen ◽  
Jichun Yu ◽  
Rong Xie ◽  
Meijun Zhong
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Cell Number ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Thyroid Cancer Cells ◽  
Dual Luciferase Reporter Assay

Objective: To explore the expression of miR-9-5p and BRAF in cisplatin resistant strain thyroid cancer cells and reversal effect of drug resistance as well as the possible mechanism. Methods: The cisplatin-resistant thyroid cancer cells (FTC-133/DDP and TPC-1/DDP) were respectively divided into 3 groups as NC, DDP and DDP + miRNA groups. Measuring cell proliferation by MTT assay and cell apoptosis by flow cytometry; Evaluating invasion cell number and wound healing rates by transwell and wound healing assay. The relative proteins (BRAF, Mek and Erk1/2) were measured by WB assay. The correlation between miR-9-5p and BRAF by dual-luciferase reporter assay in FTC-133/DDP and TPC-1/DDP cells. Results: In FTC-133/DDP and TPC-1/DDP cells experiment, compared with DDP group, with miR-9-5p supplement, the cell proliferation rats were significantly depressed with cell apoptosis increasing (P < 0.001, respectively); invasion cell number and wound healing rats were significantly down-regulation (P < 0.001, respectively) in DDP + miRNA groups. Meanwhile, the BRAF, Mek and Erk1/2 proteins expressions were significantly depressed in DDP + miRNA groups were significantly suppressed compared with those in DDP groups (P < 0.001, respectively). By dual-luciferase reporter assay, BRAF was the target gene of miR-9-5p in FTC133/DDP and TPC-1/DDP cells. Conclusion: miR-9-5p increases sensitivity to cisplatin in thyroid cancer cells by down-regulating BRAF expression.

scholarly journals hsa-miR-33-5p as a Therapeutic Target Promotes Apoptosis of Breast Cancer Cells via Selenoprotein T

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Zhuang ◽  
Jianhui Liu ◽  
Wenjin Li
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Selenoprotein T ◽  
Cancer Tissues ◽  
Mcf 7

Objective: Increasing evidence suggests that microRNA (miRNA) participates in regulating tumor cell apoptosis. We aimed to observe the effect of hsa-miR-33-5p on the apoptosis of breast cancer cells and to explore its regulatory relationship with selenoprotein T (SelT).Methods: RT-qPCR was used to examine the expression of hsa-miR-33-5p and SelT both in breast cancer tissues and cells. MCF-7 and MDA-MB-231 cells were transfected with hsa-miR-33-5p mimics or si-SelT. Then, a flow cytometry assay was carried out to examine the apoptosis of cells. Furthermore, SelT and apoptosis-related proteins including caspase-3, caspase-8, caspase-9, Bax, and Bcl-2 were detected via RT-qPCR and western blot. A luciferase reporter assay was utilized for assessing whether SelT was targeted by hsa-miR-33-5p.Results: Downregulated hsa-miR-33-5p was found both in breast cancer tissues and cells. After its overexpression, MCF-7 cell apoptosis was significantly promoted. Furthermore, our data showed that miR-33-5p elevated apoptosis-related protein expression in MCF-7 cells. Contrary to hsa-miR-33-5p, SelT was upregulated both in breast cancer tissues and cells. SelT expression was significantly inhibited by hsa-miR-33-5p overexpression. The luciferase reporter assay confirmed that SelT was a direct target of hsa-miR-33-5p. SelT overexpression could ameliorate the increase in apoptosis induced by hsa-miR-33-5p mimics.Conclusion: Our findings revealed that hsa-miR-33-5p, as a potential therapeutic target, could accelerate breast cancer cell apoptosis.

scholarly journals Embelin Enhances the Sensitivity of Renal Cancer Cells To Axitinib by Inhibiting HIF-1α Signaling Pathway

2021 ◽  
Author(s):  
Qiong Fang ◽  
Zhiying Li ◽  
Ye Xue ◽  
Xin Zong ◽  
Wenshuang Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Renal Cell ◽  
High Recurrence Rate ◽  
Urinary System ◽  
Regulatory Pathways ◽  
Targeted Drug ◽  
Clinical Drugs

Abstract Background Renal cell carcinoma (RCC) is a common malignant tumor of urinary system with high recurrence rate and easy metastasis. Current clinical drugs for renal cell carcinoma include immunotherapy and targeted drugs. Axitinib is a clinical targeted drug for the treatment of renal cell carcinoma, which has some shortcomings such as unstable efficacy and easy drug resistance. The aim of this study was to determine whether embelin can enhance the sensitivity of renal cancer cells to axitinib and explore its regulatory pathways. Results Embelin enhanced the sensitivity of renal cancer cells to axitinib in the following aspects: enhancing the inhibition of cell proliferation by axitinib, the ability to kill cancer cells, and the induction of cell apoptosis. HIF-1α was a potential pathway of Embelin action. After IOX2 regulated the HIF-1α pathway, the enhancing effect of embelin on axitinib was weakened. Conclusions Embelin enhanced the sensitivity of both A498 and 786-O renal cancer cells to axitinib by inhibiting the HIF-1α pathway.

scholarly journals miR-145 sensitizes esophageal squamous cell carcinoma to cisplatin through directly inhibiting PI3K/AKT signaling pathway

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tian-Liang Zheng ◽  
De-Ping Li ◽  
Zhan-Feng He ◽  
Song Zhao
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Akt Signaling Pathway ◽  
Cycle Arrest ◽  
Apoptotic Protein

Abstract Background Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer worldwide and is one of the most lethal malignancies. Cisplatin (DDP) is a key drug for ESCC treatment, but the presence of chemotherapy resistance limits the use of DDP. To enhance chemosensitivity to DDP is important for ESCC treatment. Methods qRT-PCR and Western blotting detected mRNA and protein expression in ESCC tissues and cells. Luciferase reporter assay assessed the interaction between miR-145 and AKT3. Cell cycle, apoptosis and proliferation were investigated with flow cytometry and MTT assay, respectively. Nude mice xenograft model was established, and immunohistochemistry (IHC) and TUNEL assay were conducted to detect Ki-67 level and apoptosis in xenograft tumor. Results Down-regulated miR-145 and up-regulated AKT3 were observed in ESCC tissues and cells. Luciferase reporter assay revealed that miR-145 negatively regulated AKT3 through binding to its 3′-UTR. Overexpression of miR-145 or knockdown of AKT3 promoted DDP-induced cell cycle arrest and apoptosis, as well as reduced IC50 of DDP treatment, which was reversed by AKT3 overexpression. The expression level of MRP1, P-gp, CyclinD1, c-Myc and anti-apoptotic protein Bcl-2 were down-regulated, while pro-apoptotic protein Bax was up-regulated by miR-145. Furthermore, overexpression of miR-145 enhanced the DDP-induced tumor growth suppression in vivo. Conclusion miR-145 increased the sensitivity of ESCC to DDP, and facilitated DDP-induced apoptosis, cycle arrest by directly inhibiting PI3K/AKT signaling pathway to decrease multidrug resistance-associated proteins MRP1 and P-gp expression. Improving the efficacy of DDP by boosting the miR-145 level provides a new strategy for treatment of ESCC.

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