Naohiko Seki

Chiba University · Department of Functional Genomics

Simple Summary Circular RNAs (circRNAs) are a new class of unique RNAs that have single-stranded, covalently closed, and continuous loop structures, which confer stability and resistance to endonuclease-mediated degradation that in turn affords substantially longer circulatory half-lives relative to linear RNAs. In this study, we established a nove...

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing from early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with differential expression using bioinformatics...

Simple Summary Based on the miRNA expression signature of LUAD, we focused on miR-139-3p, a passenger strand, and clarified its tumor-suppressive function in lung adenocarcinoma (LUAD) cells. A total of the 21 target genes (KRT80, CENPM, SPC24, ORC1, MYEOV, TRIP13, GPX8, ARHGEF39, MKI67, KIF18B, CHAF1B, CP, GPRIN1, UCK2, CHEK1, HELLS, CTSV, FAM111B...

This study aimed to identify microRNAs associated with histological grade using comprehensive microRNA analysis data obtained by next-generation sequencing in early-stage invasive breast cancer. RNA-seq data from normal breast and breast cancer samples were compared to identify candidate microRNAs with different expressions using bioinformatics. A...

Simple Summary Two passenger strand microRNAs (miRNAs), miR-30c-1-3p and miR-30c-2-3p, were identified as tumor-suppressive miRNAs in breast cancer (BrCa) cells. Seven genes (TRIP13, CCNB1, RAD51, PSPH, CENPN, KPNA2, and MXRA5) were putative targets of these miRNAs, and their expression was closely involved in BrCa molecular pathogenesis. Among the...

Lung cancer is the most common cause of cancer-related death worldwide, accounting for 1.8 million deaths annually. Analysis of The Cancer Genome Atlas data showed that all members of the minichromosome maintenance (MCM) family (hexamers involved in DNA replication: MCM2-MCM7) were upregulated in lung adenocarcinoma (LUAD) tissues. High expression...

The involvement of passenger strands of miRNAs in the molecular pathogenesis of human cancers is a recent concept in miRNA research, and it will broaden our understanding of the molecular mechanisms of miRNA-mediated cancer. The analysis of our miRNA signature of LUAD revealed that both strands of pre-miR-486 (miR-486-5p and miR-486-3p) were downre...

Coronin proteins are actin-related proteins containing WD repeat domains encoded by seven genes (CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6, and CORO7) in the human genome. Analysis of large cohort data from The Cancer Genome Atlas revealed that expression of CORO1A, CORO1B, CORO1C, CORO2A, and CORO7 was significantly upregulated in pancreatic d...

Cholinergic receptor muscarinic 3 (CHRM3)‐mediated focal adhesion kinase/YES‐associated protein (YAP) signalling is essential for the growth of castration‐resistant prostate cancer (CRPC) cells. Here, we evaluated the molecular mechanisms through which CHRM3 overexpression facilitates castration‐resistant growth. Small RNA‐sequencing combined with...

Small cell lung cancer (SCLC) is associated with a high mortality rate and limited treatment efficacy. We created a microRNA (miRNA) expression signature by RNA sequencing using specimens from patients with SCLC who had failed treatment. Forty-nine miRNAs were downregulated in SCLC tissues and were candidate tumor-suppressive miRNAs. In this signat...

The microRNA (miR) miR-874, a potential tumour suppressor, causes cell death via target gene suppression in various cancer types. Mevalonate pathway inhibition also causes cell death in breast cancer. However, the relationship between the mevalonate pathway and miR-874-induced apoptosis or its association with the tumour suppressor p53 has not been...

We recently determined the RNA sequencing-based microRNA (miRNA) expression signature of colorectal cancer (CRC). Analysis of the signature showed that the expression of both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) was significantly reduced in CRC tissues. Transient transfection assays revealed th...

Advanced-stage oral squamous cell carcinoma (OSCC) patients are treated with combination therapies, such as surgery, radiation, chemotherapy, and immunotherapy. However, OSCC cells acquire resistance to these treatments, resulting in local recurrence and distant metastasis. The identification of genes involved in drug resistance is essential for im...

Analysis of microRNA (miRNA) expression signatures in head and neck squamous cell carcinoma (HNSCC) has revealed that the miR-30 family is frequently downregulated in cancer tissues. The Cancer Genome Atlas (TCGA) database confirms that all members of the miR-30 family (except miR-30c-5p) are downregulated in HNSCC tissues. Moreover, low expression...

Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenge...

Based on our original RNA sequence-based microRNA (miRNA) signatures of head and neck squamous cell carcinoma (HNSCC), it was revealed that the expression levels of miR-1-3p, miR-206, miR-133a-3p, and miR-133b were significantly suppressed in cancer specimens. Seed sequences of miR-1-3p/miR-206 and miR-133a-3p/miR-133b are identical. Interestingly,...

Several recent studies have shown that both strands of certain miRNAs derived from miRNA duplexes are involved in cancer pathogenesis. Our own recent studies revealed that both strands of the miR-150 duplex act as tumor-suppressive miRNAs in lung adenocarcinoma (LUAD) through the targeting of several oncogenes. The aim of the study here was to furt...

Our previous study revealed that the miR-199 family (miR-199a-5p/-3p and miR-199b-5p/-3p) acts as tumor-suppressive miRNAs in head and neck squamous cell carcinoma (HNSCC). Furthermore, recent studies have indicated that the passenger strands of miRNAs are involved in cancer pathogenesis. The aim of this study was to identify cancer-promoting genes...

In humans, the coronin family is composed of seven proteins containing WD-repeat domains that regulate actin-based cellular processes. Some members of the coronin family are closely associated with cancer cell migration and invasion. The Cancer Genome Atlas (TCGA) analysis revealed that CORO1C, CORO2A, and CORO7 were significantly upregulated in or...

Background/aim: Our recent miRNA analyses revealed that miR-30a-5p has tumor-suppressive activity in pancreatic ductal adenocarcinoma (PDAC). Herein, we sought to identify tumor-suppressive genes controlled by miR-30a-5p, emphasizing on genes that are closely involved in the molecular pathogenesis of PDAC. We uncovered several novel findings regar...

We newly generated an RNA-sequencing-based microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC). Analysis of the signature revealed that both strands of some miRNAs, including miR-139-5p (the guide strand) and miR-139-3p (the passenger strand) of miR-139, were downregulated in HNSCC tissues. Analysis of The Cancer...

To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger str...

We identified the microRNA (miRNA) expression signature of head and neck squamous cell carcinoma (HNSCC) tissues by RNA sequencing, in which 168 miRNAs were significantly upregulated, including both strands of the miR-31 duplex (miR-31-5p and miR-31-3p). The aims of this study were to identify networks of tumor suppressor genes regulated by miR-31-...

Simple Summary Even today, there are no effective targeted therapies for intrahepatic cholangiocarcinoma (ICC) patients. Clarifying the molecular pathogenesis of ICC will contribute to the development of treatment strategies for this disease. In this study, we searched for the role of the miR-29-3p-family and its association with oncogenic pathway....

Acute myeloid leukemia (AML) is caused by recurrent mutations in members of the gene regulatory and signaling machinery that control hematopoietic progenitor cell growth and differentiation. Here, we show that the transcription factor WT1 forms a major node in the rewired mutation-specific gene regulatory networks of multiple AML subtypes. WT1 is f...

Simple Summary Small cell lung cancer (SCLC) is a fatal malignant tumor with a poor prognosis for patients who relapse after first-line treatment. There are few effective treatments for SCLC patients with relapse. Elucidation of the molecular network related to treatment resistance is an important issue for this disease. In this study, the molecula...

We previously found that both the guide and passenger strands of the miR-139 duplex (miR-139-5p and miR-139-3p, respectively) were downregulated in cancer tissues. Analysis of TCGA datasets revealed that low expression of miR-139-5p (p < 0.0001) and miR-139-3p (p < 0.0001) was closely associated with 5-year survival rates of patients with renal cel...

Our recent research has revealed that passenger strands of certain microRNAs (miRNAs) function as tumor-suppressive miRNAs in cancer cells, e.g., miR-101-5p, miR-143-5p, miR-144-5p, miR-145-3p, and miR-150-3p. Thus, they are important in cancer pathogenesis. Analysis of the miRNA expression signature of breast cancer (BrCa) showed that the expressi...

Simple Summary A total of 10 genes (YWHAZ, F3, TMOD3, NFE2L3, ENDOD1, ITGA3, RRAS, PRSS23, TOP2A, and LRRFIP1) were identified as tumor suppressive miR-30c-5p and miR-30c-2-3p targets in pancreatic ductal adenocarcinoma (PDAC), and expression of these genes were independent prognostic factors for patient survival. Furthermore, aberrant expression o...

Our recent studies have implicated some passenger strands of miRNAs in the molecular pathogenesis of human cancers. Analysis of the microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) has shown that levels of miR-30a-3p, the passenger strand derived from pre-mir-30a, are significantly downregulated in PDAC tissues. This...

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with approximately 650,000 new cases diagnosed annually and 400,000 HNSCC-related deaths worldwide each year. HNSCC is typically diagnosed when already at an advanced stage. Despite advancements in surgery, radiation therapy, and chemotherapy, patients with advanced HNSC...

Aberrantly expressed microRNAs (miRNAs) disrupt intracellular RNA networks and contribute to malignant transformation of cancer cells. Utilizing the latest RNA sequencing technology, we newly created the miRNA expression signature of esophageal squamous cell carcinoma (ESCC). A total of 47 miRNAs were downregulated in ESCC tissues, and these miRNAs...

RNA-sequencing-based microRNA (miRNA) expression signatures have revealed that miR-148a-5p (the passenger strand of the miR-148a-duplex) is downregulated in various kinds of cancer tissues. Analysis of The Cancer Genome Atlas (TCGA) database showed that low expression of miR-148a-5p was predictive of a lower survival rate (p = 0.041) in patients wi...

Analysis of microRNA (miRNA) regulatory networks is useful for exploring novel biomarkers and therapeutic targets in cancer cells. The Cancer Genome Atlas (TCGA) dataset shows that low expression of both strands of pre‐miR‐101 (miR‐101‐5p and miR‐101‐3p) significantly predicted poor prognosis in clear cell renal cell carcinoma (ccRCC). The function...

Aberrantly expressed microRNAs (miRNAs) are known to disrupt intracellular RNA networks in cancer cells. Exploring miRNA‐dependent molecular networks is a major challenge in cancer research. In this study, we performed RNA‐sequencing of breast cancer (BrCa) clinical specimens to identify tumor‐suppressive miRNAs in BrCa. In total, 64 miRNAs were id...

Our analyses of tumor-suppressive microRNAs (miRNAs) and their target oncogenes have identified novel molecular networks in lung adenocarcinoma (LUAD). Moreover, our recent studies revealed that some passenger strands of miRNAs contribute to cancer cell malignant transformation. Downregulation of both strands of the miR-143 duplex was observed in L...

Bladder cancer (BC) is the ninth most malignant tumor worldwide. Some BC patients will develop muscle‐invasive BC (MIBC), which has a 5‐year survival rate of approximately 60% due to metastasis. As such, there is an urgent need for novel therapeutic and diagnostic targets for MIBC. Analysis of novel antitumor‐microRNA (miRNA)‐mediated cancer networ...

Based on our miRNA expression signatures, we focused on miR-150-5p (the guide strand) and miR-150-3p (the passenger strand) to investigate their functional significance in lung adenocarcinoma (LUAD). Downregulation of miR-150 duplex was confirmed in LUAD clinical specimens. In vitro assays revealed that ectopic expression of miR-150-5p and miR-150-...

Previously, we established a microRNA (miRNA) expression signature in pancreatic ductal adenocarcinoma (PDAC) tissues using RNA sequencing and found significantly reduced expression of miR-204-5p. Here, we aimed to investigate the functional significance of miR-204-5p and to identify miR-204-5p target genes involved in PDAC pathogenesis. Cancer cel...

Our ongoing analyses identifying dysregulated microRNAs (miRNAs) and their controlled target RNAs have shed light on novel oncogenic pathways in pancreatic ductal adenocarcinoma (PDAC). The PDAC miRNA signature obtained by RNA sequencing showed that both strands of pre-miR-130b (miR-130b-5p, the passenger strand and miR-130b-3p, the guide strand) w...

In the human genome, miR-451a is encoded close to the miR-144 on chromosome region 17q11.2. Our previous study showed that both strands of pre-miR-144 acted as antitumor miRNAs and were involved in lung squamous cell carcinoma (LUSQ) pathogenesis. Here, we aimed to investigate the functional significance of miR-451a and to identify its targeting of...

Analyses of our previously determined microRNA (miRNA) expression signature of renal cell carcinoma (RCC) and The Cancer Genome Atlas (TCGA) database revealed that both strands of the pre-miR-532-duplex-miR-532-5p (the guide strand) and miR-532-3p (the passenger strand)- are closely associated with poor prognosis of RCC patients (P = 0.0411 and P =...

Fig. S1. Schematic representation of the chromosomal location of human miR‐455.

Fig. S6. IHC score and representative immunostaining pictures.

Fig. S7. Validation of si‐PIR function.

Fig. S8. Evaluation of mRNA expression of PIR using bisamide.

Fig. S3. Relationship between putative oncogenes regulated by miR‐455‐5p/‐3p and clinicopathological factors in PCa patients.

Fig. S4. Heatmaps of genes regulated by the miR‐455‐duplex and Kaplan–Meier patient survival curves for disease‐free survival rates.

Fig. S5. Direct regulation of PIR expression by miR‐455‐5p in PCa cells.

Fig. S9. Search for genes downstream of PIR.

Table S1. Patient characteristics.

Fig. S2. Incorporation of both miR‐455‐5p and miR‐455‐3p into the RISC.

Fig. S10. Kaplan–Meier curves of overall survival in other cancers due to difference in PIR expression based on TCGA database.

Table S2. Product numbers for reagents.

Table S3. Patient characteristics and IHC score evaluated using immunohistochemistry.

Table S4. Genes downregulated by si‐PIR in PCa cells.

Table S5. Genes downregulated by PIR inhibitor (bisamide) in PCa cells.

Table S6. Genes downstream of PIR.

Table S7. Trends of HSF1‐mediated gene expression in the presence of the PIR inhibitor bisamide.

Objectives To identify oncogenes regulated by micro‐ribonucleic acid, miR‐199a/b‐3p, in metastatic castration‐resistant prostate cancer. Methods Advanced ribonucleic acid sequencing technologies were applied to construct a micro‐ribonucleic acid expression signature using metastatic castration‐resistant prostate cancer autopsy specimens. Ectopic e...

Androgen deprivation therapy is frequently used to treat prostate cancer (PCa) but resistance can occur, a condition known as castration‐resistant prostate cancer (CRPC). Thus, novel approaches for identification of CRPC are important for designing effective prostate cancer (PCa) treatments. Analysis of microRNA (miRNA) expression signatures by RNA...

The prognosis of patients with advanced‐stage lung squamous cell carcinoma (LUSQ) is poor, and effective treatment protocols are limited. Our continuous analyses of antitumor microRNAs (miRNAs) and their oncogenic targets have revealed novel oncogenic pathways in LUSQ. Analyses of our original miRNA expression signatures demonstrated that both stra...

Although miR‑145‑5p (the guide strand of the miR‑145 duplex) is established as a tumor suppressive microRNA (miRNA or miR), the functional significance of miR‑145‑3p (the passenger strand of the miR‑145 duplex) in cancer cells and its targets remains obscure. In our continuing analysis of esophageal squamous cell carcinoma (ESCC) pathogenesis, the...

Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly...

Background MicroRNAs (miRNAs) belong to a group of small non-coding RNA molecules that act as pivotal agents responsible for fine-tuning RNA expression in a sequence-dependent manner. A large number of studies showed that dysregulated miRNAs are deeply involved in the development of cancer cells, as well as their metastasis and drug resistance. Bas...

Objectives: To identify key oncogenes and proteins that are controlled by the microRNA miR-29 family (miR-29a, miR-29b and miR-29c) in renal cell carcinoma pathogenesis. Methods: Genome-wide gene expression and in silico database analyses were carried out. The Cancer Genome Atlas database was used to investigate the clinical significance of gene...

Our original microRNA (miRNA) expression signatures (based on RNA sequencing) revealed that both strands of the miR-145 duplex (miR-145-5p, the guide strand, and miR-145-3p, the passenger strand) were downregulated in several types of cancer tissues. Involvement of passenger strands of miRNAs in cancer pathogenesis is a new concept in miRNA biogene...

In the human genome, miR‐451a, miR‐144‐5p (passenger strand) and miR‐144‐3p (guide strand) reside in clustered miRNA sequences located within the 17q11.2 region. Low expression of these miRNAs is significantly associated with poor prognosis of patients with renal cell carcinoma (RCC) (miR‐451a: p = 0.00305; miR‐144‐5p: p = 0.00128; miR‐144‐3p: p =...

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney, and approximately 70-80% of RCCs are classified as clear cell-type (ccRCC). Approximately 350,000 new cases are diagnosed worldwide, with over 140,000 deaths, every year. Although surgical resection remains the only known curative treatment for localized RCC, a significant percen...

Bladder cancer (BC) is a common urologic cancer and the ninth most common cause of death worldwide. In 2015, it was estimated that approximately 76,000 new cases were diagnosed as BC and 1600 patients died in United States of America. Approximately 70-80% of patients are diagnosed with non-muscle-invasive BC (NMIBC) at the first visit and high recu...

p>In developed countries, prostate cancer (PCa) is one of the most commonly diagnosed cancers, identified by prostate-specific antigen (PSA) screening; PCa is also the third leading cause of cancer-related death among men. Most naïve PCa initially responds well to androgen-deprivation therapy (ADT). However, during ADT treatment, PCa cells acquire...

MicroRNAs (miRNAs) are unique in that a single miRNA molecule regulates a vast number of RNA transcripts. Thus, aberrantly expressed miRNAs disrupt tightly controlled RNA networks in cancer cells. Our functional screening showed that expression of miR-124-3p was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues. Here, we aimed to inv...

Recent studies revealed that some passenger strands of miRNAs acted as antitumor or oncogenic miRNAs in cancer cells. In this study, we focused on miR-455- 5p (the passenger strand) and miR-455-3p (the guide strand) based on microRNA (miRNA) expression signatures of cancer cells. Both miR-455-5p and miR-455-3p were downregulated in renal cell carci...

We previously used RNA sequencing to establish the microRNA (miRNA) expression signature of pancreatic ductal adenocarcinoma (PDAC). We found that both strands of pre‐miR‐148a (miR‐148a‐5p: the passenger strand and miR‐148a‐3p: the guide strand) were downregulated in cancer tissues. Ectopic expression of miR‐148a‐5p and miR‐148a‐3p significantly in...