LIN28B/IRS1 axis is targeted by miR‐30a‐5p and promotes tumor growth in colorectal cancer

Abstract

Insulin receptor substrate 1 (IRS1) is a potential oncogene that has been implicated in several malignant tumors. However, the regulatory mechanism of IRS1 remains to be investigated. The aim of our current study is to unveil the mechanism by which IRS1 exerts functions in tumorigenesis of colorectal cancer (CRC). The expression level of IRS1 was found to be higher in CRC cells in comparison with the normal cell. To determine the role of IRS1 in regulating CRC cellular processes, loss‐of‐function assays were designed and carried out in two CRC cell lines. Both in vitro and in vivo functional assays indicated that silencing of IRS1 suppressed CRC cell survival. Based on bioinformatics prediction and mechanism experiments, IRS1 was identified as a downstream target of miR‐30a‐5p. Furthermore, RNA‐binding protein lin‐28 homolog B (LIN28B) was determined to be a stabilizer of IRS1 messenger RNA. More importantly, LIN28B also acted as a target of miR‐30a‐5p.Through rescue assays, we proved that LIN28B‐stablized IRS1 mediated miR‐30a‐5p‐mediated CRC cell growth. In conclusion, this study revealed that LIN28B and LIN28B‐stablized IRS1 promoted CRC cell growth by cooperating with miR‐30a‐5p.

miR‐30a inhibits androgen‐independent growth of prostate cancer via targeting MYBL2, FOXD1, and SOX4

“…miR‐30a has been shown to play an inhibitory role in many cancers, such as cancers of the colon, breast, and lung 38‐40 . miR‐30a has also been previously reported to function as a tumor suppressor in PCa 12,13,15,16,41 .…”

An in silico approach to identify and prioritize miRNAs target sites polymorphisms in colorectal cancer and obesity

“…In this case, the miR-30 family, miR-504, miR-34c, miR-488, miR-15b, miR-195, miR-497, miR-15a, miR-503, miR-141, miR-182, miR-96, and miR-136 were also related to invasion, proliferation, metastasis and tumor growth, or survival of several cancers including CRC. [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65] However, there are few studies on the role of included prioritized miRNAs for interactions with obesity. For obesity there are some studies on mice, for instance, miR-16-5p decrease with high weight and a mutation in miR-16 gene lead to increasing in body weight.…”

Bioinformatics Analysis of Prognostic value and prospective Pathway signal of miR-30a in Ovarian Cancer

“…More and more studies have shown that the aberrant versions of hsa-miR-30a-5p (miR-30a) are involved in the biological process of a variety of tumors. Some studies have shown that the Lin28b/IRS1 axis targeting miR-30a-5p promotes the growth of colorectal cancer (8). Liang et al (9) believes that plasma miR-30a-5p can be used as a biomarker for early diagnosis and prognosis of lung cancer.…”