The interplay between HIF-1α and noncoding RNAs in cancer

Abstract

Hypoxia is a classic characteristic of the tumor microenvironment with a significant impact on cancer progression and therapeutic response. Hypoxia-inducible factor-1 alpha (HIF-1α), the most important transcriptional regulator in the response to hypoxia, has been demonstrated to significantly modulate hypoxic gene expression and signaling transduction networks. In past few decades, growing numbers of studies have revealed the importance of noncoding RNAs (ncRNAs) in hypoxic tumor regions. These hypoxia-responsive ncRNAs (HRNs) play pivotal roles in regulating hypoxic gene expression at the transcriptional, posttranscriptional, translational and posttranslational levels. In addition, as a significant gene expression regulator, ncRNAs exhibit promising roles in regulating HIF-1α expression at multiple levels. In this review, we briefly elucidate the reciprocal regulation between HIF-1α and ncRNAs, as well as their effect on cancer cell behaviors. We also try to summarize the complex feedback loop existing between these two components. Moreover, we evaluated the biomarker potential of HRNs for the diagnosis and prognosis of cancer, as well as the potential clinical utility of shared regulatory mechanisms between HIF-1α and ncRNAs in cancer treatment, providing novel insights into tumorigenicity, which may lead to innovative clinical applications.

The emerging roles of circular RNAs in ovarian cancer

“…As well known, hypoxia plays an essential role in cancer aggressiveness and recent researches have focused on the correlation between hypoxia and circRNAs [93]. Several circRNAs have been reported to be impacted by hypoxia including circDENND4C [94], circDENND2A [95], circ-0000977 [96], and circ-0010729 [97].…”

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

“…Non-coding RNAs (ncRNAs) are characterized as a group of RNAs without any capacity to encode proteins [ 79 , 80 ] and consist of microRNAs (miRs) and long ncRNA [ 80 ]. Short 18–22 base pair long endogenous miRNAs play a key role in controlling gene expression by regulating several physiological, but also pathological processes, including carcinogenesis [ 81 ].…”

“…In addition, miRNAs have been identified as participating in the regulation of metabolic remodulating [ 82 ]. In this context, a number of hypoxia and HIF-dependent miRNAs with oncogenic and/or suppressive functions in cancer development were summarized [ 80 , 83 , 84 , 85 ]. These condensed data suggest that hypoxia is a master regulator of miRNA genes.…”

Non-Coding RNAs in Lung Tumor Initiation and Progression

“…Increased HIF-1α can initiate tumorigenesis in lung cancer, but by targeting of VHL by miR-147b [102] and HIF1AN by miR-182 [215], regulation can be reduced to prevent this initiation. HIF-1α can also modulate lncRNA HOTAIR to promote lung tumorigenesis in hypoxic conditions [249,250] and miR-210-3p to prevent HIF-1α degradation via suppression of SDHD enzymatic activity [194]. Focusing on non-coding RNA markers contributory to glucose metabolism and hypoxic response can help better understand how pathway crosstalk influences cell processes leading to tumorigenesis and progression.…”