HOXA11‐AS regulates JAK‐STAT pathway by miR‐15a‐3p/STAT3 axis to promote the growth and metastasis in liver cancer

Abstract

Background HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11‐AS), a newly identified long noncoding RNAs, is involved in the carcinogenic process of several human tumors. However, the role of HOXA11‐AS in liver cancer progression is not well understood. Materials and Methods This study used liver cancer tissues and cell lines (CSQT‐2 and HCCLM3) to explore the potential mechanism of HOXA11‐AS. Quantitative real‐time polymerase chain reaction and Western blot were applied to evaluate the bio‐molecules expression. Bioinformatics analysis, RNA pull down and luciferase report assay were applied to determine the molecules bind. MTT, transwell, and wound healing assay were used to measure the cell growth situation. Results HOXA11‐AS was highly expressed in liver cancer tissues and cell lines, which was closely related with poor prognosis in patients with liver cancer. HOXA11‐AS could act as a competing endogenous RNA for miR‐15a‐3p. Besides, miR‐15a‐3p negatively controlled its target molecule signal transducer and activator of transcription 3 (STAT3). Furthermore, a linear regression analysis and biological experiments showed a positive correlation between HOAX11‐AS and STAT3. Moreover, HOAX11‐AS overexpression activated the Janus kinase (JAK)‐STAT pathway and thus promoted the growth, migration, and invasion of liver cancer cells, which might be through regulating miR‐15a‐3p/STAT3 axis. Conclusion Our study suggested that HOAX11‐AS could regulate the JAK‐STAT signaling pathway by miR‐15a‐3p/STAT3 axis to promote the progression of liver cancer. Thus, HOXA11‐AS may be regarded as an effective biomarker with diagnostic, prognostic, and therapeutic potentials for liver cancer.

The long non-coding RNA HOXA11-AS promotes epithelial mesenchymal transition by sponging miR-149-3p in Colorectal Cancer

“…In gastric cancer, oral squamous cell carcinoma, osteosarcoma, renal cancer, hepatocellular carcinoma, breast cancer, prostate cancer and thyroid cancer, high expressions of HOXA11-AS have been found; furthermore, the upregulated expression of HOXA11-AS were associated with tumor progression and metastasis [12][13][14][17][18][19][20][21][22][23][24][25][26]. Here, we observed overexpression of HOXA11-AS in CRC tissues, and high expression of HOXA11-AS was positively correlated with more aggressive clinicopathological parameters for the first time.…”

Development of a nine‑lncRNA signature as a novel prognostic marker of estrogen receptor‑negative breast cancer

“…A number of signature lncRNAs have been reported to be associated with different types of tumor (45,46). For example, CPS1 Intronic Transcript 1 has been demonstrated to suppress cell proliferation, invasion and metastasis in colorectal, ovarian, lung and liver cancer (28)(29)(30)(31)(47)(48)(49)(50). Furthermore, upregulation of FOXD2 Adjacent Opposite Strand RNA 1 has been associated with poor prognosis in various types of tumor (51)(52)(53).…”

“…The lncRNA LINC00324 has been demonstrated to promote cell proliferation in gastric cancer by binding with human antigen R and stabilizing FAM83B expression (28). In addition, the lncRNA Homeobox A11 antisense (HOXA11-AS) regulates the JAK-STAT signaling pathway via the miR-15a-3p/STAT3 axis in order to promote liver cancer growth and metastasis (29).…”

Long Non-Coding RNAs in Liver Cancer and Nonalcoholic Steatohepatitis

“…For example, the lncRNA growth arrest specific 5 (GAS5) binds miR-21 [ 73 ], miR-23a [ 74 ], miR-135b [ 75 ], and miR-544 [ 76 ], where both miR-21 and miR-23a target the 3′-untranslated region (3′-UTR) of phosphatase and tensin homolog (PTEN) [ 73 , 74 ] ( Figure 2 D). Another example is the signal transducer and activator of transcription 3 (STAT3), which is targeted by miR-15a-3p, miR-384, and miR-4500, that, in turn, are sequestered by the lncRNA HOXA11 antisense RNA (HOXA11-AS) [ 77 ], CDKN2B antisense RNA 1 (ANRIL) [ 78 ], and small nucleolar RNA host gene 16 (SNHG16) [ 79 ], respectively ( Figure 2 E). Given that there are 1917 annotated hairpin precursors and 2654 mature sequences of human miRNAs according to the miRNA database, miRBase [ 80 ], it would not be a surprise to find intertwined networks of miRNA sponges sequestering miRNAs that target the 3′-UTR of the same gene for gene repression.…”