Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer

Li, Jian; Chen, Yuxiang; Guo, Xiong; Zhou, Ling; Jia, Zeming; Tang, Yaping; Lin, Ling; Liu, Weidong; Ren, Chao

doi:10.1007/s13277-015-4396-9

Cited by 46 publications

(46 citation statements)

References 30 publications

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“…Furthermore, miR-590-5p and miR-15b-5p were slightly but significantly elevated in the HT-29 cell line respect to non- tumour cells. Whereas it is widely known that miR-15b is elevated in samples from patients with colon cancer3233, to our knowledge, this is the first implication of miR-590-5p overexpression in colon cancer cells. Moreover, it has been demonstrated that miR-590-5p is overexpressed in renal carcinoma cell lines34, hepatocellular35 and cervical cancer tissue36.…”

Section: Discussionmentioning

confidence: 65%

Validation of suitable normalizers for miR expression patterns analysis covering tumour heterogeneity

Morata-Tarifa

Picón-Ruiz

Griñán‐Lisón

et al. 2017

Sci Rep

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Oncogenic microRNAs (miRs) have emerged as diagnostic biomarkers and novel molecular targets for anti-cancer drug therapies. Real-time quantitative PCR (qPCR) is one of the most powerful techniques for analyzing miRs; however, the use of unsuitable normalizers might bias the results. Tumour heterogeneity makes even more difficult the selection of an adequate endogenous normalizer control. Here, we have evaluated five potential referenced small RNAs (U6, rRNA5s, SNORD44, SNORD24 and hsa-miR-24c-3p) using RedFinder algorisms to perform a stability expression analysis in i) normal colon cells, ii) colon and breast cancer cell lines and iii) cancer stem-like cell subpopulations. We identified SNORD44 as a suitable housekeeping gene for qPCR analysis comparing normal and cancer cells. However, this small nucleolar RNA was not a useful normalizer for cancer stem-like cell subpopulations versus subpopulations without stemness properties. In addition, we show for the first time that hsa-miR-24c-3p is the most stable normalizer for comparing these two subpopulations. Also, we have identified by bioinformatic and qPCR analysis, different miR expression patterns in colon cancer versus non tumour cells using the previously selected suitable normalizers. Our results emphasize the importance of select suitable normalizers to ensure the robustness and reliability of qPCR data for analyzing miR expression.

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Section: Discussionmentioning

confidence: 65%

Validation of suitable normalizers for miR expression patterns analysis covering tumour heterogeneity

Morata-Tarifa

Picón-Ruiz

Griñán‐Lisón

et al. 2017

Sci Rep

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“…The ability of MTSS1 knockdown to rescue the cells from the functional consequences of Akt2 loss pointed to this scaffolding protein as a major mediator of the effects of Akt2 deficiency in CRC cells. In this regard, a role for MTSS1 in inhibition of cell proliferation and migration/invasion has been demonstrated by others in CRC cells 43,45,46 and various other cancer types. 34,64,65 However, to our knowledge, our study provides the first evidence for a pro-apoptotic function of MTSS1 in cancer cells, as indicated by the ability of MTSS1 knockdown to rescue GEO and CBS cells from the cell death-inducing effects of Akt2 knockdown.…”

Section: Discussionmentioning

confidence: 74%

“…Although the mechanism for suppression of MTSS1 mRNA by Akt2 remains to be determined, based on evidence that MTSS1 is a target for miR-23a, miR-135a, miR-135b and miR-15b in CRC cells, all of which have been implicated in promoting metastasis in diverse in vitro and in vivo experimental models, it is possible that microRNAs mediate the effect. 42,43,45,46 Consistent with this possibility, Akt isoforms have been shown to differentially regulate the expression of multiple microRNAs involved in the epithelial/ mesenchymal transition, cell motility, invasion and metastasis. Akt2 was shown to decrease the abundance of miR200 family members in breast cancer cells, promoting epithelial/mesenchymal transition and enhanced cell migration and tumor progression.…”

Section: Discussionmentioning

confidence: 80%

Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis

et al. 2017

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Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.

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“…In the present study, the expression of miR-15 was decreased in the majority of colon cancer tissues compared with para-cancerous tissues, supporting the role of miR-15 as a tumour suppressor in colon cancer. miR-15 is able to regulate chemoresistance in addition to regulating cell proliferation, apoptosis, angiogenesis and metastasis (30)(31)(32)(33). Xia et al (34) identified that miR-15 may enhance the sensitivity of gastric cancer cells to anticancer drugs by targeting BCL2 and promoting apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis

et al. 2017

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Abstract. Overcoming chemoresistance is a challenge in clinical treatment. It has been reported that microRNAs (miRNAs) are involved in regulating chemosensitivity. Therefore, the present study aimed to identify the effect and mechanism of miR-15 on colon cancer chemotherapy. Reverse transcription-quantitative polymerase chain reaction was performed to measure miR-15 level sin62-paired colon cancer and para-cancerous colon tissues. The overexpression of miR-15 in HCT116 cells was induced by transfection. The effect of miR-15 on the chemosensitivity of colon cancer cells to 5-fluorouracil (5-FU) and Oxaliplatin (OX) was determined using a luminescent cell viability assay. Flow cytometry, dual-luciferase assay and western blot analysis were used to determine the potential mechanism of miR-15. The results suggested that the expression of miR-15 was decreased in tumour tissues and that overexpression of miR-15 increased the chemosensitivity of colon cancer cells to 5-Fu and OX. miR-15 promoted apoptosis in colon cancer cells treated with 5-Fu and OX by inhibiting the expression of p50, which repressed the expression of B cell lymphoma-2 and B cell lymphoma-extra large; two direct target genes of nuclear factor-κB with anti-apoptotic functions. Thus, the current study demonstrated that miR-15 increased the chemosensitivity of colon cancer cells to 5-FU and OX by inhibiting the NF-κB signalling pathway and inducing apoptosis.

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Inhibition of miR-15b decreases cell migration and metastasis in colorectal cancer

Cited by 46 publications

References 30 publications

Validation of suitable normalizers for miR expression patterns analysis covering tumour heterogeneity

Validation of suitable normalizers for miR expression patterns analysis covering tumour heterogeneity

Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis

Overexpression of microRNA-15 increases the chemosensitivity of colon cancer cells to 5-fluorouracil and oxaliplatin by inhibiting the nuclear factor-κB signalling pathway and inducing apoptosis

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