MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

Wang, Yihui; Tang, Qingchao; Li, Mingqi; Jiang, Shuang; Wang, Xishan

doi:10.1016/j.bbrc.2014.01.028

Cited by 99 publications

(79 citation statements)

References 23 publications

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“…All animal procedures were performed in accordance with Harbin Medical University Institutional Animal Care and Use Committee guidelines. The animals were housed as described previously (8). A total of 5 ϫ 10 6 HCT116 cells that were stably transfected with miR-30a were injected subcutaneously to the right flank of nude mice.…”

Section: Methodsmentioning

confidence: 99%

“…Total cell or tissue extracts were extracted in cell lysis buffer, followed by immunoblotting with anti-IRS2 (1:1,000; Abcam, Cambridge, MA), anti-AKT (1:1,000; Cell Signaling Technology, Danvers, MA), anti-phospho-AKT (anti-p-AKT; 1:2,000) (Cell Signaling Technology, Danvers, MA), anti-STAT3 (1:1,000; Cell Signaling Technology, Danvers, MA), anti-p-STAT3 (1:1,000; Cell Signaling Technology, Danvers, MA), and anti-␤-actin (1:2,000; Santa Cruz Biotechnology, Santa Cruz, CA) as described previously (8). A Bio-Rad ChemiDoc MP system was used for Western blot imaging.…”

Section: Methodsmentioning

confidence: 99%

“…miRNAs are involved in a plethora of biological processes, such as proliferation, migration, invasion, and apoptosis (3,4). In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer, including CRC (5)(6)(7)(8).…”

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confidence: 99%

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Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Zhang

Tang

Qin

et al. 2015

Molecular and Cellular Biology

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d MicroRNAs (miRNAs) are dysregulated in many types of malignant diseases, including colorectal cancer. miRNA 30a (miR-30a) is a member of the miR-30 family and has been implicated in many types of cancers. In this study, we determined the expression of miR-30a in human colon cancer tissues and cell lines. miR-30a was found to be significantly downregulated in both the tissues and cell lines. Furthermore, overexpression of miR-30a inhibited, while silencing of miR-30a promoted, cell proliferation, migration, and invasion in vitro. Consistently, stable overexpression of miR-30a suppressed the growth of colon cancer cell xenografts in vivo. Moreover, bioinformatic algorithms and luciferase reporter assays revealed that insulin receptor substrate 2 (IRS2) is a direct target of miR-30a. Further functional studies suggested that repression of IRS2 by miR-30a partially mediated the tumor suppressor effect of miR-30a. In addition, miR-30a inhibited constitutive phosphorylation of Akt by targeting IRS2. Additionally, clinicopathological analysis indicated that miR-30a has an inverse correlation with the staging in patients with colon cancer. Taken together, our study provides the first evidence that miR-30a suppressed colon cancer cell growth through inhibition of IRS2. Thus, miR-30a might serve as a promising therapeutic strategy for colon cancer treatment. Colorectal cancer (CRC) is the third most common cancer in males and females, with an estimated 142,820 new cases and 50,830 deaths in the United States in 2013. The overall CRC incidence is 5% in the general population, and the 5-year survival rate ranges from 40% to 60% (1). Despite the improvement of currently available treatment strategies, including surgical resection, radiotherapy, and chemotherapy, the survival rate of patients with CRC has changed little over the past 10 years. Almost 50% of CRC patients will die of the disease, mainly due to metastasis to the liver. Thus, it is imperative to achieve earlier diagnosis and better tailoring of treatments to improve CRC outcomes.MicroRNAs (miRNAs) are a family of endogenous small noncoding RNAs that regulate gene expression via the sequence-specific base pairing on the 3= untranslated regions (3= UTRs) of target mRNAs, resulting in mRNA cleavage or translation inhibition (2). More than 30% of the protein-coding genes are controlled by miRNAs, as indicated by bioinformatics predictions. miRNAs are involved in a plethora of biological processes, such as proliferation, migration, invasion, and apoptosis (3, 4). In recent years, miRNAs have been recognized as critical regulators in development and progression of cancer, including CRC (5-8).miRNA 30a (miR-30a) is a member of the miR-30 family, which consists of six distinct mature miRNA sequences: miR-30a/ miR-30c-2, miR-30d/miR-30b, and miR-30e/miR-30c-1 (9). There is considerable evidence suggesting that the dysregulation of miR-30a is correlated with several types of malignant tumors, including breast cancer, lung cancer, thyroid cancer, gastric cancer, and leuke...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Zhang

Tang

Qin

et al. 2015

Molecular and Cellular Biology

Self Cite

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“…Recently, many miRNAs have been reported to regulate cancer carcinogenesis by targeting PIK3CA, including miR-19a [34], miR-134 [35]; miR-203 [36], miR-375 [22,37]; miR-422a [38], miR-490-5p [39], et al In this study, PIK3CA was found as a direct target of miR-148a-3p by bioinformatics analysis, luciferase reporter assay and western blot. Moreover, PIK3CA were involved in inhibitory effects of miR-148a-3p on cell proliferation, migration and invasion in OS.…”

Section: Discussionmentioning

confidence: 70%

MiR-148a-3p suppresses cell proliferation, migration and invasion by targeting PIK3CA in human osteosarcoma cells

Wang¹,

Zhou²,

Zhao³

et al. 2018

Oncotarget

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Osteosarcoma (OS) is the most common type of primary malignant bone tumor and is characterized by complex genetic changes and resistance to conventional treatments. In this study, the role of miR-148a-3p in the progression and metastasis of OS was investigated. Firstly, it was found that the expression of miR-148a-3p was down-regulated in OS tissues and cell lines compared with that in adjacent non-neoplastic bone tissues and OS cell line. In addition, it was found that miR148a-3p inhibited cell proliferation, migration and invasion in MG-63 and U2OS cells and tumorigenicity in nude mice. Meanwhile, bioinformatic analysis suggested that phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) gene is a potential target of miR-148a-3p. Then, it was found that PIK3CA can be directly regulated by miR-148a-3p via luciferase assay and western blot assay. Furthermore, PIK3CA knockdown induced effects on OS cell lines similar to those induced by miR-148a-3p. Taken together, these data suggest that miR-148a-3p suppresses cell proliferation, migration and invasion and PIK3CA was involved in miR-148a-3p associated biological functions in OS. Commonly down-regulated miR148a-3p may act as a tumor suppressor and a novel therapeutic strategy by downregulating PIK3CA expression.

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“…Therefore, the aberrant expression of miRNAs may lead to cellular dedifferentiation, oncogenesis, cancer metastasis and tumor invasion (6). An increasing number of miRNAs have been revealed to be involved in the growth and metastasis of CRC, including miRNA-27a (7,8), miRNA-145 (9,10), miRNA-29 (11), miRNA-221 (12), miRNA-96 (13) and miRNA-375 (14). miRNA-103 (miR-103), which belongs to the miR-103/107 family, is capable of inducing epithelial-to-mesenchymal transition (EMT) of mammary epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2

Zheng

Xiao

et al. 2016

Oncology Letters

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Abstract. Colorectal cancer (CRC) has become the third most common cancer worldwide and leads to a high mortality rate. Although colorectal cancer has been studied widely, the underlying molecular mechanism remains unclear. Increasing evidence shows that the abnormal expression of microRNAs (miRNAs) is involved in tumorigenesis. Previous studies have reported that miRNA-103 (miR-103) is dysregulated in CRC; however, the expression, function and mechanism of miR-103 in CRC are not well known. The present study showed that miR-103 was overexpressed in the primary tumor tissues of patients with CRC and was significantly associated with a more aggressive phenotype of CRC in patients. Survival rate analysis demonstrated that CRC patients with high miR-103 expression had a poorer overall survival compared with CRC patients with low miR-103 expression. In CRC cell lines, miR-103 inhibition significantly decreased the proliferation, invasion and migration of the cells in vitro. Furthermore, miR-103 repressed large tumor suppressor kinase 2 (LATS2) expression by directly binding to the LATS2-3'-untranslated region, and an inverse correlation was identified between the expression of miR-103 and LATS2 messenger RNA in primary CRC tissues. In addition, the restoration of LATS2 led to suppressed proliferation, invasion and migration of CRC cells. In vivo, miR-103 promotes tumor growth in nude mice. In summary, miR-103 performs a critical role in the promotion of the invasive and metastatic capacities of CRC, possibly by directly targeting LATS2. This miRNA may be involved in the development and progression of CRC.

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MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

Cited by 99 publications

References 23 publications

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

Role of MicroRNA 30a Targeting Insulin Receptor Substrate 2 in Colorectal Tumorigenesis

MiR-148a-3p suppresses cell proliferation, migration and invasion by targeting PIK3CA in human osteosarcoma cells

MicroRNA-103 promotes tumor growth and metastasis in colorectal cancer by directly targeting LATS2

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