Novel reciprocal interaction of lncRNA HOTAIR and miR‐214‐3p contribute to the solamargine‐inhibited PDPK1 gene expression in human lung cancer

Abstract

Solamargine (SM) has been shown to have anti‐cancer properties. However, the underlying mechanism involved remains undetermined. We showed that SM inhibited the growth of non‐small cell lung cancer (NSCLC) cells, which was enhanced in cells with silencing of long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), while it overcame by overexpression of HOTAIR. In addition, SM increased the expression of miR‐214‐3p and inhibited 3‐phosphoinositide‐dependent protein kinase‐1 (PDPK1) gene expression, which was strengthened by miR‐214‐3p mimics. Intriguingly, HOTAIR could directly bind to miR‐214‐3p and sequestered miR‐214‐3p from the target gene PDPK1. Intriguingly, overexpression of PDPK1 overcame the effects of SM on miR‐214‐3p expressions and neutralized the SM‐inhibited cell growth. Similar results were observed in vivo. In summary, our results showed that SM‐inhibited NSCLC cell growth through the reciprocal interaction between HOTAIR and miR‐214‐3p, which ultimately suppressed PDPK1 gene expression. HOTAIR effectively acted as a competing endogenous RNA (ceRNA) to stimulate the expression of target gene PDPK1. These complex interactions and feedback mechanisms contribute to the overall effect of SM. This unveils a novel molecular mechanism underlying the anti‐cancer effect of SM in human lung cancer.

Exosomal circEIF3K from cancer-associated fibroblast promotes colorectal cancer (CRC) progression via miR-214/PD-L1 axis

“…MiR-214 has been shown to inhibit cancer cell phenotypes through interacting with lncRNAs, circRNAs or others [ 32 , 33 ]. In this study, miR-214 was confirmed to bind circEIF3K and could rescue circEIF3K-mediated CRC progression, which was in agreement with prior findings.…”

LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells

“…Our studies clearly highlight the significance of miRNA-214 and HOTAIR signatures in treatment of cervical cancer. For example, the combination of miR-214 overexpression and paclitaxel treatment might be more effective in the treatment of cervical cancer than paclitaxel alone [ 32 ]. At present, some RNA-based approaches have been developed to target ncRNAs, including antisense oligonucleotides (ASOs) or siRNAs.…”

“…Many miRNAs (let-7b, let-7c, miR-21, miR-23b, miR-196b, miR-143, miR-126-3p, miR-20b-5p, miR-451a, and miR-144-3p) were identified as potential biomarkers for cervical cancer diagnosis, prognosis and cancer stage, even have been shown effective for diagnosis of cervical adenocarcinoma and high grade intraepithelial lesions [ 29 , 30 ]. MiR-214-3p was a miRNA involved in many cancer, including lung cancer, breast cancer, colon cancer, endometrial carcinoma, and pancreatic cancer in humans [ 31 , 32 ]. In cervical cancer, miR-214-3p has been found play an important roles in regulating cell proliferation, apoptosis, cell invasion, metastasis and angiogenesis [ 33 , 34 ].…”

Non-coding RNAs in cancer: platforms and strategies for investigating the genomic “dark matter”

“…The ncRNAs have cell type, tissue and cancer specificity, thus RNA profiling has become a mean to identify useful biomarkers of tumor development, progression and metastasis. Although miRNAs represent the most widely investigated ncRNAs, lncRNAs are emerging as cancer key regulators [7,12]. Arrays and next generation sequencing (NGS) are high-throughput methods to detect and quantify ncRNAs, even though several caveats are to be considered.…”