Long noncoding RNA Linc00339 promotes triple‐negative breast cancer progression through miR‐377‐3p/HOXC6 signaling pathway

Abstract

Recently, long noncoding RNAs (lncRNAs) have become the key gene regulators and prognostic biomarkers in various cancers. Through microarray data, Linc00339 was identified as a candidate oncogenic lncRNA. We compared the expression levels of Linc00339 in several breast cancer cell lines and normal mammary gland epithelial cell line. The effects of Linc00339 on tumor progression were examined both in vitro and in vivo. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays were applied to evaluate the functions of Linc00339, miR‐377‐3p, and HOXC6 on cell proliferation. Flow cytometry analysis was used to detect apoptosis and cell cycle distribution. Overall survival (OS) was analyzed using data from The Cancer Genome Atlas and molecular taxonomy of breast cancer international consortium (METABRIC). Dual luciferase assay and RNA immunoprecipitation were performed to confirm the interaction between Linc003339 and miR‐377‐3p. Linc00339 was increased in breast cancer cell lines compared with the normal epithelial cell. Through in vitro and in vivo experiments, Linc00339 overexpression promoted triple‐negative breast cancer (TNBC) proliferation, inhibited cell cycle arrest, and suppressed apoptosis. Silencing of Linc00339 obtained the opposite effects. Mechanistic investigations demonstrated that Linc00339 could sponge miR‐377‐3p and regulate its expression. Higher expression of miR‐377‐3p indicated longer OS in breast cancer patients, especially in TNBC patients. Overexpression of miR‐377‐3p retarded TNBC cell growth through regulating cell cycle distribution and apoptosis. And miR‐377‐3p was involved in Linc00339‐mediated TNBC proliferation through regulating HOXC6 expression. Knockdown of HOXC6 inhibited TNBC progression. In conclusion, our results illuminated that the novel Linc00339/miR‐377‐3p/HOXC6 axis played a critical role in TNBC progression and might be a promising therapeutic target for TNBC treatment.

<p>LINC00339 promotes growth and invasiveness of hepatocellular carcinoma by the miR-1182/SKA1 pathway</p>

“…23 Previous studies have reported that LINC00339 is the sponge for miR-377-3p, miR-145, and miR-539-5p. [12][13][14] This work for the first time identified LINC00339 as the sponge for miR-1182. To date, knowledge about miR-1182 is poor.…”

“…21 Recently, several researchers have demonstrated that LINC00339 promotes proliferation, migration, and invasion of laryngeal squamous cell carcinoma and breast cancer. 13,14 Its role in HCC remains limitedly studied. We provided evidence that LINC00339 promotes HCC tumorigenesis and metastasis through the miR-1182/ SKA1 pathway.…”

“…Previously, researchers have shown that LINC00339 promotes the development of glioma and laryngeal squamous cell carcinoma. [12][13][14] However, the roles of LINC00339 in HCC are unclear. Our research indicated that LINC00339 was upregulated in HCC tissues.…”

Dysregulated lncRNA-miRNA-mRNA Network Reveals Patient Survival-Associated Modules and RNA Binding Proteins in Invasive Breast Carcinoma

“…Five of these molecules have been shown to play important roles in breast cancer. For example, Wang et al, (2019b) reported that overexpression of miR-377 correlates with better prognosis in triple-negative breast cancer. ADAMTS-5 may alter the cellular microenvironment, affecting the balance between protumor and antitumor effects (Fontanil et al, 2017).…”

Systematic characterization of non‐coding RNAs in triple‐negative breast cancer

“…Similarly, lncRNA TROJAN promoted the proliferation of TNBC cells by inducing ZMYND8 degradation 92 . LINC00339 regulated TNBC cell growth by promoting proliferation and inhibiting apoptosis via regulation of miR‐377‐3p/HOXC6 expression 93 . Moreover, there are also some non‐classical lncRNA‐involved mechanisms in the regulation of TNBC progression.…”