Infrequently expressed miRNAs influence survival after diagnosis with colorectal cancer

Abstract

Half of miRNAs expressed in colorectal tissue are expressed < 50% of the population. Many infrequently expressed miRNAs have low levels of expression. We hypothesize that less frequently expressed miRNAs, when expressed at higher levels, influence both disease stage and survival after diagnosis with colorectal cancer (CRC); low levels of expression may be background noise.We examine 304 infrequently expressed miRNAs in 1893 population-based cases of CRC with paired carcinoma and normal mucosa miRNA profiles. We evaluate miRNAs with disease stage and survival after adjusting for age, study center, sex, MSI status, and AJCC stage. These miRNAs were further evaluated with RNA-Seq data to identify miRNA::mRNA associations that may provide insight into the functionality of miRNAs.Eleven miRNAs were associated with advanced disease stage among colon cancer patients (Q value = 0.10). Eight infrequently expressed miRNAs influenced survival if highly expressed in overall CRC. Of these, five increased likelihood of dying if they were highly expressed, i.e. miR-124-3p, miR-143-5p, miR-145-3p, miR31-5p, and miR-99b-5p, while three were associated with better survival if highly expressed, i.e. miR-362-5p, miR-374a-5p, and miR-590-5p. Thirteen miRNAs infrequently expressed in colon-specific carcinoma tissue were associated with CRC survival if highly expressed. Evaluation of miRNAs::mRNA associations showed that mRNA expression influenced by infrequently expressed miRNA contributed to networks and pathways shown to influence disease progression and prognosis.Our large study enabled us to examine the implications of infrequently expressed miRNAs after removal of background noise. These results require replication in other studies. Confirmation of our findings in other studies could lead to important markers for prognosis.

Long noncoding RNA MIR31HG is a bona fide prognostic marker with colorectal cancer cell‐intrinsic properties

“…High miR‐31‐5p expression has previously been established as a poor prognostic factor in pCRC . Here we provide evidence that MIR31 is a high‐risk biomarker beyond known molecular subgroups, major gene expression phenotypes as well as tumor immune and stromal cell infiltration.…”

“…We have previously reported that miR‐31‐5p has oncogenic properties in CRC cell lines and in primary CRC (pCRC), elevated miR‐31‐5p expression has important clinicopathological and molecular associations, including advanced cancer stage, right‐sided tumor localization, sessile serrated adenoma, low differentiation grade, micro‐satellite instability (MSI) and mutated BRAF and KRAS . Furthermore, high expression levels have been associated with poor outcome in stage I–IV pCRCs …”

Circulating microRNA‐590‐5p functions as a liquid biopsy marker in non‐small cell lung cancer

“…Scale bar, 100 μm and n = 3 NSCLC tissues 2), TGF-βRII (transforming growth factor beta receptor 2), 23 NF90/ VEGFA (nuclear factor 90/vascular endothelial growth factor A) 20,21 and GAB1 (GRB2 associated binding protein A) 39 which promote cancer growth and progression. 22,26,27,40,41 Likewise, miR-590-5p oncogenic properties were reported in gastric, cervical, vulvar, and clear cell renal cancer, where it targets RECK (reversion inducing cysteine rich protein with kazal motifs), 32 CHL1 (close homolog of L1), 28 TGF-βRII, 29 and PBRM1 (Polybromo 1), 30 respectively, and regulates cell proliferation, migration and invasion of cancer cells. However, the role of circulating miR-590-5p in blood plasma has not been reported.…”

“…Recently, cellular miR‐590‐5p has been shown to play important roles in tumorigenesis and metastasis of various cancers where it was shown to function as either a tumor suppressor or an oncomiR based on its target(s) in the respective cancers. Its expression was found to be downregulated in breast, hepatocellular, colorectal, and lung cancer tissues, and targeted the Wnt/β‐catenin pathway, SOX2 (SRY‐box 2), TGF‐βRII (transforming growth factor beta receptor 2), NF90/VEGFA (nuclear factor 90/vascular endothelial growth factor A) and GAB1 (GRB2 associated binding protein A) which promote cancer growth and progression . Likewise, miR‐590‐5p oncogenic properties were reported in gastric, cervical, vulvar, and clear cell renal cancer, where it targets RECK (reversion inducing cysteine rich protein with kazal motifs), CHL1 (close homolog of L1), TGF‐βRII, and PBRM1 (Polybromo 1), respectively, and regulates cell proliferation, migration and invasion of cancer cells.…”

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

“…Furthermore, regulation of transforming growth factor α gene expression by miR-374a inhibited the proliferation, migration and invasion of lung adenocarcinoma cells (31). Slattery et al (32) demonstrated that the expression levels of miR-374a were downregulated in colorectal cancer, whereas low miR-203 expression levels were associated with worse clinicopathological data and shorter OS time. However, Xu et al (33) reported that miR-374a acts as a tumor promoter in gastric cancer, where it and promotes cell proliferation, migration and invasion via the regulation of SRC kinase signaling inhibitor 1 expression levels.…”