miR-202 Diminishes TGFβ Receptors and Attenuates TGFβ1-Induced EMT in Pancreatic Cancer

Mody, Hardik R.; Hung, Sau Wai; Pathak, Rakesh; Griffin, Jazmine; Cruz‐Monserrate, Zobeida; Govindarajan, Rajgopal

doi:10.1158/1541-7786.mcr-16-0327

Cited by 38 publications

(33 citation statements)

References 30 publications

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“…Moses et al reported that TGFβ binds to the heterodimeric type II and type I TGF‐β serine/threonine kinase receptors (TGFBR2 and TGFBR1) and initiates a signaling cascade through phosphorylation of SMAD2 and SMAD3 . TGFBR1 promoted cell proliferation, migration and invasion in lung cancer, pancreatic cancer, and glioblastoma . In this study, we reported that TGFBR1 promoted cell proliferation, migration, invasion and the cell cycle and inhibit cell apoptosis in HeLa and C33A cells.…”

Section: Discussionmentioning

confidence: 56%

DANCR‐mediated microRNA‐665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway

et al. 2019

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Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)‐665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR‐665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR‐665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR‐665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR‐665 and mediated the ERK/SMAD pathway. In addition, we identified miR‐665 as the competing endogenous RNA for long noncoding (lnc)‐DANCR. These observations suggested that lnc‐DANCR‐mediated miR‐665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.

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Section: Discussionmentioning

confidence: 56%

DANCR‐mediated microRNA‐665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway

et al. 2019

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“…In human ESCCs, miR-202 regulated apoptosis by targeting HSF2 via mechanism involving caspase-3. A study also identified that miR-202 plays an important role in regulating cell proliferation, migration and invasion of cervical cancer (CC) by directly targeting cyclin D1, and miR-202 may represent a potential therapeutic target for patients with CC (16)(17)(18)(19)(20)(21)(22). In addition, a previous study showed that an increased serum concentration of miR-202 may be a strong independent prognostic factor for breast cancer patients (20).…”

Section: Discussionmentioning

confidence: 99%

miR‑202 acts as a potential tumor suppressor in breast cancer

et al. 2018

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Abstract. Breast cancer affects ~10% of women worldwide and is responsible for ~12% of all cancer-associated mortalities. Breast cancer is more prone to metastasis compared with other types of cancer. Up to 5% of patients with breast cancer present with incurable metastasis and an additional 10-15% of patients develop metastases within 3 years of their initial diagnosis. MicroRNAs (miRNAs) are short RNAs, 21-25 nucleotides in length, that have been shown to significantly affect gene expression. In total >2,000 miRNAs have been identified and specific miRNAs have been revealed to be associated with cancer. In the present study, we observed that the majority of breast cancer specimens collected expressed low levels of miR-202 compared with adjacent tissues and normal cell lines. Mechanistic investigations identified KRAS as a potential target gene of miR-202 and it was demonstrated that miR-202 exerted its tumor-suppressive effects by regulating the expression of KRAS in breast cancer cells. Functional assays revealed that miR-202 significantly reduced cell proliferation, migration and invasion in vitro. In summary, these results indicate the function of miR-202 in breast cancer progression and suggest that its use within breast cancer therapy is promising. IntroductionBreast cancer is one of the most common malignant tumors in women. In many areas, breast cancer is the most common malignancy in females. In China, the incidence of breast cancer is increasing annually. Because the development and progression of breast cancer are complex processes involving many genes, the underlying mechanism of breast cancer remains unclear (1,2).Single-stranded RNAs consisting of 19 to 25 nucleotides are known as microRNAs (miRNAs). These RNAs are regulatory molecules that modulate the expression of functional genes, play an important role in many biological processes, and are expressed in a tissue-and time-specific manner. miRNAs regulate gene expression at the post-transcriptional level mainly via completely complementary or partially complementary binding to the 3' UTR of the target gene, resulting in degradation or translational repression of the target gene (2-4). Studies have shown that a variety of miRNAs are involved in malignant transformation processes, such as malignant proliferation, metastasis and recurrence, and apoptosis inhibition. Studies have reported that miRNA inhibitors can reduce the high miR-21 expression in breast cancer cells, inhibiting proliferation and migration; that miR-373 can promote the metastasis of breast cancer cells; that miR-520 plays a role in promoting the development of breast cancer; and that miR-126 and miR-335 are able to inhibit breast cancer to a certain extent (5-7). Recent studies have demonstrated that miR-202 is associated with several types of cancer, miR-202 has a lower expression in several of cancers, and however, the expression and function of miR-202 have not been investigated in breast cancer (8).KRAS belongs to the RAS family; it is located on the short arm of chromosome 1...

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“…As one of three TGF‐β receptors, TGFBR1 can regulate signal transduction rate through phosphorylating downstream Smad‐2 and Smad‐3 . Experimental studies have shown that TGFBR1 can promote malignant proliferation and metastasis of tumors by regulating epithelial‐mesenchymal transformation . Rosman et al and Zhou et al also revealed similar outcomes that TGFBR1*6A could promote the invasion and metastasis of MCF‑7 breast cancer cells and colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 89%

Prognostic value of transforming growth factor beta receptor 1 polymorphisms in patients with oral cancer

Chen

Wang

et al. 2019

J Oral Pathology Medicine

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Objective: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1). Methods:Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer.Results: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed.Conclusions: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings. K E Y W O R D Soral cancer, prospective study, radiotherapy, TGFBR1

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miR-202 Diminishes TGFβ Receptors and Attenuates TGFβ1-Induced EMT in Pancreatic Cancer

Cited by 38 publications

References 30 publications

DANCR‐mediated microRNA‐665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway

DANCR‐mediated microRNA‐665 regulates proliferation and metastasis of cervical cancer through the ERK/SMAD pathway

miR‑202 acts as a potential tumor suppressor in breast cancer

Prognostic value of transforming growth factor beta receptor 1 polymorphisms in patients with oral cancer

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