The microRNA-202 as a Diagnostic Biomarker and a Potential Tumor Suppressor

Abstract

MicroRNA-202 (miR-202) is a member of the highly conserved let-7 family that was discovered in Caenorhabditis elegans and recently reported to be involved in cell differentiation and tumor biology. In humans, miR-202 was initially identified in the testis where it was suggested to play a role in spermatogenesis. Subsequent research showed that miR-202 is one of the micro-RNAs that are dysregulated in different types of cancer. During the last decade, a large number of investigations has fortified a role for miR-202 in cancer. However, its functions can be double-edged, depending on context they may be tumor suppressive or oncogenic. In this review, we highlight miR-202 as a potential diagnostic biomarker and as a suppressor of tumorigenesis and metastasis in several types of tumors. We link miR-202 expression levels in tumor types to its involved upstream and downstream signaling molecules and highlight its potential roles in carcinogenesis. Three well-known upstream long non-coding-RNAs (lncRNAs); MALAT1, NORAD, and NEAT1 target miR-202 and inhibit its tumor suppressive function thus fueling cancer progression. Studies on the downstream targets of miR-202 revealed PTEN, AKT, and various oncogenes such as metadherin (MTDH), MYCN, Forkhead box protein R2 (FOXR2) and Kirsten rat sarcoma virus (KRAS). Interestingly, an upregulated level of miR-202 was shown by most of the studies that estimated its expression level in blood or serum of cancer patients, especially in breast cancer. Reduced expression levels of miR-202 in tumor tissues were found to be associated with progression of different types of cancer. It seems likely that miR-202 is embedded in a complex regulatory network related to the nature and the sensitivity of the tumor type and therapeutic (pre)treatments. Its variable roles in tumorigenesis are mediated in part thought its oncogene effectors. However, the currently available data suggest that the involved signaling pathways determine the anti- or pro-tumorigenic outcomes of miR-202’s dysregulation and its value as a diagnostic biomarker.

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

“…However, they also reported that higher levels of let-7f were reported in patients with more malignant tumours [ 31 ]. Multiple studies demonstrated the tumour suppressive properties of the miR-202, and a connection between its decreased expression and tumour development [ 103 ]. On the other hand, Monastirioti et al observed that increased serum miR-202 expression correlated with poor survival in patients with advanced stage NSCLC [ 49 ].…”

“…Let-7 is a family of miRNAs, which was initially discovered in Caenorhabditis elegans [ 101 , 102 ]. In humans it was shown to control the stem-cell division and differentiation [ 101 ] and supress the tumour development through various pathways [ 39 , 103 , 104 ]. It has been demonstrated that the let-7 miRNAs could be used as predictive and prognostic markers in patients with lung cancer [ 7 , 25 ].…”

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“…The system of proper gene transcription regulation is disturbed in the altered cell. In contrast to how miRNA targets a specific oncogene in a healthy cell by suppressing it when the miRNA gene is silenced, the oncogene output experiences enhanced expression ( Ahmed et al, 2022 ; Uzuner et al, 2022 ). The tumor suppressor is effectively hindered by uncontrolled amplification of the miRNA gene that modulates it, which also induces carcinogenesis.…”

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“…The oncogene PTEN plays important roles in cell growth, apoptosis, adhesion, migration, and infiltration. PTEN is an evaluation indicator for the prognosis of numerous tumors, and the study of its mechanism of action is important for tumors diagnosis and gene therapy ( Ahmed et al, 2022 ). Lu et al observed that sorafenib combined with 20(S)-Rg3 significantly reduced the viability of human HCC cell lines HepG2 and Huh7, promoted apoptosis, increased chemotherapy sensitivity, and reversed chemoresistance by modulating the PTEN/Akt signaling pathway.…”