MicroRNAs that regulate PTEN as potential biomarkers in colorectal cancer: a systematic review

Abstract

Purpose: MicroRNAs (miRNAs) participate in a variety of biological processes, including tumorigenesis, progression, invasion, and drug resistance to multiple cancers. Phosphatase and tensin homolog (PTEN) is a cancer suppressor gene that has been certified to be regulated by miRNAs in various tumors, including colorectal cancer (CRC). In this review, we screened articles focusing on low PTEN expression in CRC, observed the expression of related miRNAs, analyzed their correlation and relationship with clinicopathological features, and discussed the possibility of these miRNAs as prognostic molecules.

Methods: We conducted a systematic search for articles published in the Web of Science, PubMed and EBSCO databases between January 1, 2002, and July 18, 2019. We identified these studies by using combinations of the following index entries and key words: 'colorectal tumor OR colorectal neoplasm OR colorectal carcinoma OR colorectal cancer OR CRC', 'protein tyrosine phosphatase OR PTEN', and 'microRNA OR MiRNA OR miRNA OR MicroRNA'. Moreover, we evaluated the underlying association between alterations in PTEN and CRC prognosis.

Results: PTEN expression was obviously lower in CRC tissues than in normal mucosa. However, PTEN expression did not differ significantly between adenoma and normal tissues. PTEN tends to be negatively associated with tumor size and metastasis. MiR-21, miR-200a, miR-543, miR-32, miR-92a, miR-26a, miR-106a and miR-181a were correlated with the downregulation of PTEN. MiR-26a, miR-106a and miR-181a were obviously higher in CRC tissues than in normal tissues, while PTEN was downregulated in CRC tissues. Additionally, miRNAs were mainly positively correlated with distant metastasis, followed by TNM stage. The relationship between miRNAs and tumor differentiation is controversial. However, there were no significant differences between miRNAs and either sex or age.

Conclusions: The loss of PTEN may be a diagnostic factor for CRC patients. The above-mentioned miRNAs may function as oncogenes in CRC and represent potential targets for CRC therapy. However, further prospective clinical studies are necessary.

Keywords: Biomarker; Colorectal cancer (CRC); Diagnosis; MicroRNAs (miRNAs); Phosphatase and tensin homolog (PTEN); Prognosis.

Fig. 1

The role of PTEN in the PI3K/AKT pathway

Fig. 2

Systematic literature search flowchart

Fig. 3

MiRNAs as biomarkers in CRC with low PTEN expression. Compared with normal adjacent tissues, CRC tissues with low PTEN expression were first screened. To observe which miRNAs affect CRC formation by regulating PTEN, we further observed the differential expression of miRNAs

Fig. 4

The expression of miRNA-21 in PTEN-downregulated CRC and normal tissues

Fig. 5

Kaplan–Meier curves for various survival rates in patients with CRC. No association was found between PTEN expression and the overall survival, relapse-free survival or metastasis-free survival of CRC patients (P > 0.05)