Downregulation of microRNA-1274a induces cell apoptosis through regulation of BMPR1B in clear cell renal cell carcinoma

Yoshino, Hirofumi; Yonezawa, Tomokazu; Yonemori, Masaya; Miyamoto, Kazuaki; Sakaguchi, Takashi; Sugita, Satoru; Osako, Youichi; Tatarano, Shuichi; Nakagawa, Masayuki; Enokida, Hideki

doi:10.3892/or.2017.6098

Cited by 18 publications

(17 citation statements)

References 23 publications

(35 reference statements)

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“…As the most common type of adult kidney cancer, ccRCC is characterized by poor prognosis and a high risk of metastasis and recurrence (29). Epigenetic modifications, including RNA modification (21,22,24), DNA methylation (30), histone modification (31) and microRNA changes (32,33), serve diverse functions in the malignant progression and prognosis of ccRCC. As the most prevalent type of internal RNA modification, m6A RNA methylation has gained increasing attention over the past decade (5,7,8,12).…”

Section: Discussionmentioning

confidence: 99%

N6‑methyladenosine RNA methylation regulators participate in malignant progression and have prognostic value in clear cell renal cell carcinoma

et al. 2020

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N 6-methyladenosine (m6A) RNA methylation is the most prevalent type of mRNA modification; however, little is known about its function in clear cell renal cell carcinoma (ccRCC). The present study aimed to establish and validate a m6A-related risk signature as a prognostic factor for patients with ccRCC. Consensus clustering was used to divide patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort (n=489) into three clusters (cluster 1/2/3) based on 19 m6A RNA methylation regulators. In addition, a m6A-related risk signature was constructed using TCGA data, and its accuracy was validated using data from the International Cancer Genome Consortium (n=91). The prognostic performance of the risk signature was evaluated by Kaplan-Meier analyses, least absolute shrinkage and selection operator Cox regression, multivariate Cox regression, receiver operating characteristic curves and nomograms. The results revealed that the majority of the 19 m6A RNA methylation regulators were differentially expressed among ccRCC stratified by different clinicopathological features. The cluster 1 group exhibited a higher frequency of metastasis and poorer overall survival compared with the cluster 2/cluster 3 group. The hallmarks of RNA metabolism, transcription misregulation in cancer and regulation of autophagy, were significantly enriched in the cluster 1 group. A m6A-related risk signature was constructed and validated with high prognostic accuracy for the prediction of 5-year survival and recurrence (area under the curve, 0.736 and 0.728, respectively). The present study also established robust nomograms for evaluating the risk of mortality and recurrence for patients with ccRCC (c-index, 0.783 and 0.819, respectively). The dysregulation of hub m6A RNA methylation regulator expression levels and m6A RNA methylation levels were also validated in multiple RCC cells using in vitro experiments. Taken together, the m6A RNA methylation regulators promoted the malignant progression of ccRCC and exhibited good performance in prognostic predictions. These results provided insight into the development of m6A-targeted treatments for ccRCC.

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Section: Discussionmentioning

confidence: 99%

N6‑methyladenosine RNA methylation regulators participate in malignant progression and have prognostic value in clear cell renal cell carcinoma

et al. 2020

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“…An increasing number of previous studies have demonstrated that miRNAs are dysregulated in approximately all types of human malignancy, including ccRCC (13)(14)(15). miRNA (miR)-19a (16), miR-224 (17), miR-1274a (18) and miR-543 (19) were upregulated in ccRCC, whereas, miR-30a (20), miR-200a (21), miR-384 (22) and miR-411 (23) were downregulated. These aberrantly expressed miRNAs are implicated in the oncogenesis and progression of ccRCC, and regulate various crucial biological processes, including cell proliferation, apoptosis, metastasis and angiogenesis (13,24).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑663 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells by directly targeting PAK4

2018

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Accumulating evidence has demonstrated that microRNAs (miRNAs) are key gene regulators and are abnormally expressed in clear cell renal cell carcinoma (ccRCC). The dysregulation of miRNAs has been implicated in the initiation and progression of ccRCC. Therefore, identification of ccRCC-associated miRNAs may facilitate the determination of promising therapeutic targets for anti-cancer treatment.In the present study, miRNA-663 (miR-663) expression was downregulated in ccRCC tissues and cell lines. Functional experiments suggested that restoration of miR-663 expression inhibited the proliferation and invasion of ccRCC cells. In addition, p21 activated kinase 4 (PAK4) was validated as a direct target of miR-663 in ccRCC cells. PAK4 was upregulated in ccRCC tissues, and the expression level of PAK4 was inversely correlated with the miR-663 expression level. PAK4 restoration partially attenuated the suppressive roles of miR-663 overexpression on the proliferation and invasion of ccRCC cells. The present results provide novel insight into the mechanism underlying the occurrence and development of ccRCC, suggesting that the miR-663/PAK4 axis may be a novel therapeutic target for treatment of patients with ccRCC.

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“…There is no study in the literature investigating the role of miR-1260a, and miR-1260b miRNA molecules in ovarian cancer. The expression level of miR-1260a was investigated in breast, kidney, gastric cancer, malignant melanoma, hepatocellular carcinoma, colorectal carcinoma, and esophageal squamous cell carcinoma, and was detected to have been upregulated in these cancers [23][24][25][26][27][28][29][30]. In addition, miR-1260a expression level was reported to have high level expression in the serum, and FFPE tissues of prostate cancer patients compared with the BPH controls, and higher expression was also reported in prostate cell strains [31,32,62].…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs were shown to cause functional changes in cancer cells, and therefore had roles in various cancers [21]. miR-1260a was shown to be located on 14q24.3 chromosome region, and this miRNA was upregulated in breast cancer, malignant melanoma, hepatocellular carcinoma, colorectal carcinoma, esophageal squamous cell carcinoma, kidney carcinoma, and gastric cancer [22][23][24][25][26][27][28][29]. Although there was no study in the literature suggesting that miR-1260a was speci cally associated with ovarian cancer, miR-1260a was suggested to have possibly been upregulated in ovarian cancer in the assumption after the results of the study investigating that in prostate cancer patients [28] [30].…”

Section: Introductionmentioning

confidence: 99%

High Expression Level of miR-1260 Family in the Peripheral Blood of Patients with Ovarian Carcinoma

Ghafour

Ödemiş

Tunçer

et al. 2020

Preprint

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The most common gynecologic cancers detected in women in Turkey are uterine cancer, ovarian cancer, and cervical cancer. These data reported that a mean of 3800 individuals were diagnosed with uterine cancer, 2790 were diagnosed with ovarian cancer, and 1950 were diagnosed with cervical cancer, and 400 individuals were diagnosed with other gynecologic cancers each year in Turkey. A mean of 14.270 individuals were detected to have been diagnosed with gynecologic cancers each year in the United States of America(USA). Ovarian cancer treatment is generally composed of chemotherapy, and surgery. In general, chemotherapy is administered after surgery. The identification of the molecular pathogenesis of ovarian cancer, and discovery of new moleculer biomarkers which facilitate the ovarian cancer treatment are required for an effective ovarian cancer treatment in clinics. miRNAs are reported to be the possible biologic indicators for various cancer types. We aimed to investigate 2 miRNAs which were suggested to have effect in ovarian cancer in our (previous)monozygotic twin study from miR-1260 microRNA family whose association with ovarian cancer yet has not been reported in the literature. We investigated the expression levels of miR-1260a, and miR-1260b miRNAs, in the peripheral blood lymphocytes of 150 familial and sporadic ovarian cancer patients, and of 100 healthy individuals of the control group who were matched for age, sex, and ethnicity with the patient group, and investigated their possible property of being a biologic indicator for ovarian cancer. The expression results of ovarian cancer patients were evaluated by comparison of the results of the control group in the study. The expression levels of miR-1260a, and miR-1260b in ovarian cancer patients were found highly increased compared with the levels in the control group. miR-1260a expression level in ovarian cancer patients was detected to have increased approximately 17 fold compared with the control group, and miR-1260b expression level in ovarian cancer patients was detected to have increased approximately 33 fold compared with the levels in the control group. The String Analyses showed that the miR-1260a was associated with the ribosomal protein family which was known to be effective in the translation stage of cell and that miR-1260b was associated with CHEK2 protein which was a member of the serine/threonine-protein kinase family. It should be investigated for larger cohorts in benign ovarian diseases and in different stages of patients receiving ovarian cancer treatment whether these two molecules are a noninvasive biomarker and therapeutic target to be used especially in the early diagnosis and prognosis of ovarian cancer in future.

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Downregulation of microRNA-1274a induces cell apoptosis through regulation of BMPR1B in clear cell renal cell carcinoma

Cited by 18 publications

References 23 publications

N6‑methyladenosine RNA methylation regulators participate in malignant progression and have prognostic value in clear cell renal cell carcinoma

N6‑methyladenosine RNA methylation regulators participate in malignant progression and have prognostic value in clear cell renal cell carcinoma

MicroRNA‑663 inhibits the proliferation and invasion of clear cell renal cell carcinoma cells by directly targeting PAK4

High Expression Level of miR-1260 Family in the Peripheral Blood of Patients with Ovarian Carcinoma

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