Down regulation of miR-202 modulates Mxd1 and Sin3A repressor complexes to induce apoptosis of pancreatic cancer cells

Farhana, Lulu; Dawson, Marcia I.; Fontana, Joseph A.

doi:10.4161/15384047.2014.987070

Cited by 36 publications

(41 citation statements)

References 46 publications

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“…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). Mutations in KRAS lead to sustained activation of the RAS protein, independent of EGFR/HER receptor activation, and eventually cause abnormalities in the RAS signaling pathway.…”

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…2 An increasing number of studies have demonstrated that miRNAs play critical roles in several tumor-related biological processes, including cell proliferation, apoptosis, migration, and invasion. 3,4 Dysregulated miRNA expression is involved in the development of cancer, and miRNAs can be used as diagnostic or prognostic biomarkers. 5 Thus, exploring the novel regulators of tumorigenesis may have benefits for early diagnostics and for understanding the underlying molecular mechanism.…”

Section: Introductionmentioning

confidence: 99%

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2

Yun

Deng

et al. 2016

Cancer Biology & Therapy

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This study aimed to understand the exact function and potential mechanism of miR-4500 in colorectal cancer (CRC). In this study, the expression of miR-4500 was decreased in both CRC cells and tissues, and downregulated miR-4500 indicated advanced tumor stage and poor survival. By bisulfite sequencing analysis, we found that the CpG island in the promoter region of miR-4500 was hypermethylated in CRC cells and tissues compared with normal control cells and non-tumor tissues, respectively. Functionally, gain-and loss-of-function analyses indicated the tumor suppressor role of miR-4500: it suppressed cell proliferation, cell cycle progression, migration, and invasion. Predictive algorithms and experimental analyses identified HMGA2 as a direct target of miR-4500. Reintroducing HMGA2 impaired the inhibitory effects of miR-4500 on cell growth and motility. Clinically, higher HMGA2 protein expression in CRC tissues was associated with advanced tumor stage and poor survival. An inverse correlation was found between miR-4500 levels and HMGA2 protein expression. Taken together, this study provides the first evidence that miR-4500 functions as a novel tumor suppressor in the miR-4500/HMGA2 axis in colorectal carcinogenesis, and restoring miR-4500 expression might represent a promising therapeutic strategy for CRC.Abbreviations: CRC, Colorectal cancer; HMGA2, high mobility group AT-hook 2; 5-aza, 5-aza-2 0 -deoxycytidine

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“…Other studies indicate a physiological association between increases in follicular miRNA levels and hormone secretion levels in mammals, which involved signaling pathways involved in follicular cell proliferation, steroidogenesis, prevention of premature luteinization, and oocyte maturation (Sontakke et al, 2014;Donadeu et al, 2016;Xie et al, 2016). miR-202 inhibits tumor progression and (Farhana et al, 2015;Lin et al, 2016;Meng et al, 2016) affects the immune system (Fornari et al, 2015;Owen et al, 2015). miRNAs regulate levels of expression of target genes by controlling the signal pathways (Š ahmatova et al, 2016;Wang et al, 2016).…”

Section: Discussionmentioning

confidence: 94%

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

Liu

Zhao

et al. 2017

DNA and Cell Biology

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In recent years, with the need of the fur industry to obtain greater quantities of high-quality fur and the research of hair follicle development attracting greater attention, the role of miRNAs in hair follicle development has become a field of intense interest. miRNAs are short length RNAs that affect gene regulation by binding to the 3'-untranslated region (3'UTR) of the mRNAs of certain target genes. This study predicted and validated the target genes of miR-202 in the skin tissue of C57BL/6 black mice and BALB/c white mice. The expression of miR-202 target genes (wnt5a, kit, and tcf7) was examined by real-time quantitative polymerase chain reaction and western blot in the mouse skin tissue and human embryonic kidney 293T cells (HEK293T cells) which overexpress miR-202. The luciferase reporter gene system was used to verify the correlation between the expression of miR-202 and its putative target genes. We show that the expression of miR-202 was higher in the skin tissue of C57BL/6 black mice than in the skin tissue of BALB/c white mice (p < 0.05). Furthermore, the expression of wnt5a, kit, and tcf7 was observed to be negatively correlated with the expression of miR-202 and to be downregulated by miR-202 in vitro and in vivo. The luciferase reporter gene system indicated that the target sequences of miR-202 are present in 3'UTR of wnt5a, kit, and tcf7 mRNAs. Altogether, this study has shown that the expression of miR-202 was different in the skin tissue of C57BL/6 black mice and BALB/c white mice and that wnt5a, kit, and tcf7 are negatively regulated by miR-202.

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Down regulation of miR-202 modulates Mxd1 and Sin3A repressor complexes to induce apoptosis of pancreatic cancer cells

Cited by 36 publications

References 46 publications

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

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

MiR-4500 is epigenetically downregulated in colorectal cancer and functions as a novel tumor suppressor by regulating HMGA2

Differential Expression of miR-202 and Validation of Predicted Target Genes in the Skin Tissue of C57BL/6 Black Mice and BALB/c White Mice

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