Cancer

bladder cancer

Regulation

downregulation

Reporting

microRNA 99a acts as a tumor suppressor and is down regulated in bladder cancer. We used Taqman probe stem-loop real-time PCR to accurately measure the levels of miR-99a in bladder cancer cell lines 100 pairs of bladder cancer tissues the adjacent non-neoplastic tissues and plasma collected from bladder cancer patients or control patients. miR-99a was significantly down-regulated in bladder cancer tissues and even the lower expression of miR-99a was correlative with the more aggressive phenotypes of bladder cancer. Furthermore investigation of the expression of miR-99a in plasma of bladder cancer patients showed that miR-99a was also decreased in plasma of bladder cancer patients. The results strongly supported miR-99a as the potential diagnostic marker of bladder cancer. Our data indicated that miR-99a might act as a tumor suppressor in bladder cancer and was significantly down-regulated in development of bladder cancer

Pubmed

24957100

Method

qPCR

Cancer

bladder cancer

Regulation

downregulation

Reporting

Cell free urinary microRNA 99a and microRNA 125b are diagnostic markers for the non invasive screening of bladder cancer. MicroRNA profiles of the urine supernatants of UCB patients and controls without any malignancy and profiles of malignant and corresponding normal mucosa tissues from the patients were determined by microRNA microarray and compared to identify differentially expressed microRNAs. The differential expression was verified in the tissues of an independent patient cohort by RT-qPCR. MicroRNA-99a and microRNA-125b were down-regulated in the urine supernatants of UCB patients. A diagnostic model was developed using a combined index of the levels of microRNA-99a and microRNA-125b in the urine supernatant with a sensitivity of 86.7% a specificity of 81.1% and a positive predicted value PPV of 91.8%. An effective cell-free urinary microRNA-based model was developed using a combined index of the levels of microRNA-99a and microRNA-125b to detect UCB with good discriminating power high sensitivity and high specificity

Pubmed

25014919

Method

Microarray; qPCR

Cancer

bladder cancer

Regulation

downregulation

Reporting

In the first - discovery - phase microarray cards with 381 miRNAs were used for miRNA analysis of 13 controls and 46 bladder cancer patients. In the second - verification - phase the results of this first phase were verified on the same groups of subjects by single-target qPCR assays for the selected miRNAs. For the third - validation - phase new independent samples of urine supernatant 23 controls and 27 bladder cancer patients were analyzed using single-target qPCR assays for 13 verified in the previous phase. The results of all phases were normalized to miR-191 miR-28-3p and miR-200b which were selected as suitable for our study by the qBase+®.We found that miR-125b miR-30b miR-204 miR-99a and miR-532-3p are significantly down-regulated in patients' urine supernatant. In our experiments the analysis of miR-125 levels provided the highest AUC 0.801 with 95.65% specificity and 59.26% sensitivity the analysis of miR-99a lead to AUC 0.738 with 82.61% specificity and 74.07% sensitivity

Pubmed

27468885

Method

Microarray; qPCR

Cancer

breast cancer

Regulation

downregulation

Reporting

miR-99a has been reported as a tumor suppressor gene in various cancers in humans. However only limited information about the function of miR-99a in human breast cancers is available. Here we investigated the expression of miR-99a in breast cancer tissue specimens and its antitumor activity in breast cancer cells. More importantly we found downregulation of miR-99a in breast cancer specimens from ten different patients. We then analyzed the mechanism of miR-99a in inhibiting tumorigenesis

Pubmed

24637915

Method

Cancer

breast cancer

Regulation

downregulation

Reporting

Based on microarray data we identified miR-99a as a potential tumor suppressor in breast cancer. Expression of miR-99a is frequently down-regulated in breast cancer tissues relative to normal breast tissues. Reduced miR-99a expression was highly associated with lymph node metastasis and shorter overall survival of patients with breast cancer. Gain- and loss-of-function studies revealed that miR-99a significantly inhibits breast cancer cell proliferation migration and invasion. Collectively our data indicate that miR-99a plays a tumor-suppressor role in the development of breast cancer and could serve as a potential therapeutic target for breast cancer treatment

Pubmed

26417931

Method

Microarray

Cancer

breast cancer

Regulation

downregulation

Reporting

Low levels of serum miR 99a is a predictor of poor prognosis in breast cancer. Although miR-99a is aberrantly expressed in many types of cancers including breast cancer the serum miR-99a expression level in breast cancer and its clinical significance remains unknown. Blood samples were obtained from 72 patients with breast cancer and 40 healthy volunteers and subjected to real-time polymerase chain reaction to evaluate the level of expression of serum miR-99a in the study participants. Furthermore we investigated the association between serum miR-99a and the clinical outcome of breast cancer. Serum miR-99a expression was significantly downregulated in patients with breast cancer compared to that in healthy controls P < 0.01. Moreover the serum miR-99a was correlated with various clinical parameters of breast cancer including lymph node metastasis P = 0.0194 distant metastasis P = 0.0037 Ki67 intensity P = 0.0164 TNM stage P = 0.0096 and histological grade P = 0.0051 of cancer. Additionally breast cancer patients displaying lower miR-99a levels showed poorer overall survival rates P = 0.0411. The serum miR-99a level was also found to be an independent risk factor for breast cancer hazard ratio = 3.176 95% confidence interval = 1.543-7.360 P = 0.023. Our data indicated that serum miR-99a expression was downregulated in breast cancer patients; moreover this downregulation was associated with poor prognosis suggesting that serum miR-99a could function as a tumor suppressor in breast cancer

Pubmed

27706621

Method

qPCR

Cancer

cervical and endocervical cancer

Regulation

downregulation

Reporting

Here we showed that miR-99a and -99b miR-99a/b were down-regulated in human cervical cancer patient tissues and were negatively related with lymphatic metastasis

Pubmed

24668416

Method

Cancer

colon cancer

Regulation

downregulation

Reporting

Among the miRNAs demonstrating the largest fold up- or down-regulated changes ≥4 four novel miR-31 miR-1 miR-9 and miR-99a and two previously reported miR-137 and miR-135b miRNAs were identified in the normal/adenoma comparison. All but one of these miR-99a demonstrated similar expression differences in the two normal/carcinoma comparisons suggesting that these early tumor changes are important in both the pMMR- and dMMR-derived cancers

Pubmed

21694772

Method

Cancer

esophageal cancer

Regulation

downregulation

Reporting

In this study we focused on miR-99a and miR-100 which were determined to be universally downregulated in esophageal squamous cell carcinoma and investigated their functions and potential mechanisms of action. The downregulation of miR-99a/100 was validated by qRT-PCR in 101 ESCC surgical tissue samples and in 3 ESCC cell lines

Pubmed

23292834

Method

qPCR

Cancer

gastric cancer

Regulation

deregulation

Reporting

miRNA expression signature was first analyzed by real-time PCR on 10 paired gastric carcinomas and confirmed in another 20 paired gastric carcinoma tissues. Sixteen miRNAs were upregulated in gastric carcinoma including miR-223 miR-21 miR-23b miR-222 miR-25 miR-23a miR-221 miR-107 miR-103 miR-99a miR-100 miR-125b miR-92 miR-146a miR-214 and miR-191 and six miRNAs were downregulated in gastric carcinoma including let-7a miR-126 miR-210 miR-181b miR-197 and miR-30aa-5p

Pubmed

21628394

Method

qPCR

Cancer

head and neck cancer

Regulation

downregulation

Reporting

To explore circulating miRNAs as cancer therapy biomarkers we initially identified that 8 miRNAs were distinctly dysregulated in cancerous tissues compared with adjacent non-cancerous counterparts from 16 patients using microarray and real-time PCR. MiR-99a which was down-regulated in cancerous tissues was significantly increased in plasma after operation. We firstly report the significant changes of miR-99a in plasma of HNSCC patients after surgery

Pubmed

25950115

Method

qPCR; Microarray

Cancer

kidney renal cell cancer

Regulation

downregulation

Reporting

MicroRNA 99a induces G1 phase cell cycle arrest and suppresses tumorigenicity in renal cell carcinoma. MicroRNA-99a miR-99a a potential tumor suppressor is downregulated in several human malignancies. The expression and function of miR-99a however have not been investigated in human renal cell carcinoma RCC so far. We therefore examined the expression of miR-99a in RCC cell lines and tissues and assessed the impact of miR-99a on the tumorigenesis of RCC. MiR-99a levels in 40 pairs of RCC and matched adjacent non-tumor tissues were assessed by real-time quantitative Reverse Transcription PCR qRT-PCR. The effects of miR-99a were then assessed by cell proliferation cell cycle transwell and colony formation assay. A murine xenograft model of RCC was used to confirm the effect of miR-99a on tumorigenicity in vivo. Potential target genes were identified by western blotting and luciferase reporter assay. We found that miR-99a was remarkably downregulated in RCC and low expression level of miR-99a was correlated with poor survival of RCC patients. Moreover intratumoral delivery of miR-99a could inhibit tumor growth in murine xenograft models of human RCC

Pubmed

23173671

Method

Reverse transcription PCR; qPCR

Cancer

kidney renal cell cancer

Regulation

downregulation

Reporting

Conversely decreased expression of miR-106b miR-99a miR-1826 miR-215 miR-217 miR-187 miR-129-3p miR-23b miR-27b and miR-126 was associated with a worse prognosis

Pubmed

26416448

Method

Cancer

liver cancer

Regulation

downregulation

Reporting

MicroRNA 99a inhibits hepatocellular carcinoma growth and correlates with prognosis of patients with hepatocellular carcinoma. In our in-depth analysis carried out by the Illumina Solexa massive parallel signature sequencing microRNA-99a miR-99a was found to be the sixth abundant microRNA in the miRNome of normal human liver but was markedly down-regulated in hepatocellular carcinoma HCC. However the biological function of miR-99a deregulation in HCC remains unknown. In this study we found that miR-99a was remarkably decreased in HCC tissues and cell lines. Importantly lower miR-99a expression in HCC tissues significantly correlated with shorter survival of HCC patients and miR-99a was identified to be an independent predictor for the prognosis of HCC patients. Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly inhibited tumor growth and reduced the α-fetoprotein level in HCC-bearing nude mice. Conclusively miR-99a expression was frequently down-regulated in HCC tissues and correlates with the prognosis of HCC patients thus proposing miR-99a as a prospective prognosis predictor of HCC miR-99a suppresses HCC growth by inducing cell cycle arrest suggesting miR-99a as potential tumor suppressor for HCC therapeutics

Pubmed

21878637

Method

RNA-Seq

Cancer

lung cancer

Regulation

downregulation

Reporting

miR-99a is frequently downregulated in various types of human malignancies including lung adenocarcinoma. However the underlying mechanisms involved in the modulation of invasion and migration by miR-99a remain elusive. In this study we analyzed the relationship between the expression of miR-99a and clinical stage or metastasis in 90 matched lung adenocarcinoma and adjacent non-tumor lung tissues. Downregulation of miR-99a was significantly associated with advanced stage and tumor metastasis in lung adenocarcinoma patients and it was found to be a poor prognostic factor in lung adenocarcinoma. Moreover overexpression of miR-99a significantly inhibited tumor growth in vivo

Pubmed

26986073

Method

Cancer

lung squamous cell cancer

Regulation

downregulation

Reporting

Recently several studies have shown that miR-99a is downregulated in various cancers which can affect tumor initiation and maintenance. Herein we found that miR-99a was downregulated in NSCLC tissues and suppressed tumor metastasis of NSCLC cells. Down-regulation of miR-99a is significantly associated with last-stage and tumor metastasis in NSCLC patients

Pubmed

25187230

Method

Cancer

lung squamous cell cancer

Regulation

downregulation

Reporting

miRNA-99a miR-99a which is downregulated in several human malignancies has been reported as a potential tumor suppressor. However to the best of our knowledge the expression and function of miR-99a has not been investigated in human non-small cell lung cancer NSCLC at present. The aim of the current study was to evaluate the association between NSCLC and miR-99a miR-99a expression was analyzed in 15 pairs of NSCLC and non-cancerous tissue samples by reverse transcription-quantitative polymerase chain reaction. It was found that the level of miR-99a expression was significantly downregulated in NSCLC tissues and that ectopic overexpression of miR-99a significantly inhibited the growth of A549 and H1299 cells. Additionally ectopic overexpression of miR-99a inhibited A549 and H1299 cell migration and invasion by inhibiting epithelial to mesenchymal transition. The downregulation of insulin-like growth factor 1 receptor IGF-1R by miR-99a and knockdown of IGF-1R mediated by siRNA were each found to phenocopy the effect of miR-99a overexpression in NSCLC. To the best of our knowledge the present study demonstrated for the first time that in NSCLC miR-99a is downregulated and thus regulates proliferation colony formation and migration through the IGF-1R pathway which indicates that miR-99a is a diagnostic biomarker for NSCLC

Pubmed

25663868

Method

qPCR

Cancer

sarcoma

Regulation

deregulation

Reporting

The most significantly downregulated miRNAs were miR-99a miR-200 family miR-199b-5p miR-100 and miR-335 whereas kshv-miR-K12-4-3p kshv-miR-K12-1 kshv-miR-K12-2 kshv-miR-K12-4-5p and kshv-miR-K12-8 were significantly upregulated

Pubmed

24027049

Method