MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2

Afshar, Saeid; Najafi, Rezvan; Pashaki, Abdolazim Sedighi; Sharifi, Mohammadreza; Nikzad, Safoora; Gholami, Mohammad Hadi; Khoshghadam, Alireza; Amini, Razieh; Karimi, Jamshid; Saidijam, Massoud

doi:10.1016/j.biopha.2018.07.002

Cited by 38 publications

(28 citation statements)

References 41 publications

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“…In multiple studies, it has been shown that suppression of IGF‐1R ROS‐mediated overactivation leads to the decreased radioresistance of different cancers both in vitro and in vivo (Denduluri et al, ; Moreno‐Acosta et al, ; Panganiban & Day, ; Venkatachalam et al, ; Yavari et al, ). In this regard, findings from Afshar () study have shown that inhibition of IGF‐1R by ectopic increase of miR‐185 suppressed radiation‐induced IGF‐1R phosphorylation/overactivation and introduced apoptosis and then radiosensitivity in CRC cell line. Hence, blocking the IGF‐1R pathways and subsequent inhibition of involving proteins and regulatory factors could reduce cancer survival, invasion, metastasis, and also resistance to radiation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, three online databases for miRNA target prediction Master Mix (Exiqon), respectively. We carried out primer design according to Afshar et al (2018) procedure. Analysis of data was done by normalizing with internal controls GAPDH and U6, and the relative expression of genes was plotted using the ΔC t method.…”

Section: Prediction Of Mirna Target Genementioning

confidence: 99%

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Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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Abnormal expression of various microRNAs (miRNAs), as regulators of biological signaling pathways, has a strong association with cancer resistance to chemotherapy and radiotherapy. The let‐7 family of miRNAs as tumor suppressors have shown to be downregulated in different types of human malignancies including colorectal cancer (CRC). However, the biological function of let‐7 members in the processes of resistance to radiation in CRC has not yet been completely elucidated. Insulin‐like growth factor 1 receptor (IGF‐1R) signaling pathway is amplified in CRC and leads to its progression, development, and also radiation resistance. So, it seems like an attractive target for anticancer therapy. In this study, by using bioinformatics analysis, it has been revealed that IGF‐1R is a direct target of the let‐7e member. Consistent with this, we identified that increased levels of let‐7e in CRC cells reduced IGF‐1R protein level and subsequently its downstream signaling pathways, which resulted in the G1 cell cycle arrest and a significant reduction in the proliferation, survival and also resistance to radiation of CRC cells. Altogether, these results suggested that let‐7e by targeting the IGF‐1R signaling pathway might serve as therapeutics in anticancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Prediction Of Mirna Target Genementioning

confidence: 99%

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Samadi

Afshar

Amini

et al. 2018

Journal Cellular Physiology

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“…24 MiR-185-3p is a mature miRNA from 3ʹ end of pre-miR-185, and the study demonstrated that miR-185, which is involved in DC-SIGN-LEF1 /TCF1-miR-185 feedback loop, regulates the invasion and metastasis of CRC 25 and can also enhance the radiosensitivity of CRC cells. 26 The function of miR-185 in CRC has been extensively explored; however, the role of miR-185-3p in CRC, especially in 5-FU resistance, has been relatively less reported. Early study found that miR-185-3p inhibits cell growth through modulating the cellular growth signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

Zhou

Kong

et al. 2020

Cancer Biology & Therapy

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Background: Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman's correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR. Results: We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic. Conclusion: MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.

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“…MicroRNAs (miRNAs) are a class of short, non-coding single stranded RNA molecules (20-24 nucleotides) that regulate gene expression by post-transcriptional silencing of target mRNAs (mRNAs) through complementary binding and they also lead to translation of some target mRNAs [17][18][19][20]. In humans, miRNAs play a substantial role in the regulation of biologic processes such as development, differentiation, cell proliferation and apoptosis [17,18,21].…”

Section: Introductionmentioning

confidence: 99%

Serum and Stool miR-135b Levels as a Potential Diagnostic Biomarker for Colorectal Cancer

Saidijam¹,

Taherikalani²,

Shabab³

et al. 2020

CEI

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Background: By considering the high incidence and mortality rate of colorectal cancer (CRC), finding the noninvasive biomarker for detection of patients with cancer is the main purpose of more and more cancer studies. Methods: In this research, the expression level of miR-135b in serum and stool of patients with colorectal cancer was investigated as a diagnostic marker. Using the real-time PCR, the relative expression level of miR-135b in serum and stool in 40 patients with colorectal cancer, paired with 40 healthy controls, was determined. Then its sensitivity and specificity were rated, via ROC curves analysis. Results: Expression levels of miR-135b in serum and stool of CRC patients were 32.4 and 15.7 times higher in serum and stool, compared to that of healthy control respectively (P<0.05). ROC curves analysis exhibited that serum miR-135b levels were powerful in detecting CRC patients from control subjects, with a sensitivity of 92.7% and a specificity of 89.7% (AUC: 0.929). In addition, stool miR-135b levels strongly distinguished CRC patients from control subjects with a sensitivity of 92.7% and a specificity of 87.2% (AUC: 0.919). Conclusions: The results of the current study indicate that serum and stool miR-135b expression levels seem to be used as a potential diagnostic biomarker for CRC patients. However further studies with large sample size are needed for approving the miR-135b as a noninvasive diagnostic biomarker of CRC.

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MiR-185 enhances radiosensitivity of colorectal cancer cells by targeting IGF1R and IGF2

Cited by 38 publications

References 41 publications

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

Let‐7e enhances the radiosensitivity of colorectal cancer cells by directly targeting insulin‐like growth factor 1 receptor

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

Serum and Stool miR-135b Levels as a Potential Diagnostic Biomarker for Colorectal Cancer

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